The Lord is called mary's "firstborn" (Matt. 1:25 and Luke 2:7), and the natural inference is that Mary had other children.  The word prototokos is used only in these two passages and in Rom. 8:29;  Col. 1:15, 18;  Heb. 1:6;  11:28;  12:23 (pl.);  Rev. 1:5, so that the meaning is easily ascertained.  Had He been her only son, the word would have been monogenes, which occurs in Luke 7:12;  8:42;  9:38, of human parentage; and of the Lord, as the only begotten of the Father, in John 1:14, 18;  3:16, 18;  1John 4;9.  In Heb. 11:17 it is used of Isaac, Abraham's only son according to the promise.

In Psalm 69, a Psalm with many predictive allusions to the Lord's earthly life (see Note on Title), verse 8 reads, "I am become a stranger unto my brethren, and an alien unto my mother's children".   The Gospel history records His brethren in association with His mother.  After the miracle at Cana, which they probably witnessed, we are told that "He went down to Capernaum, He, and His mother, and His brethren, and His disciples" (John 2:12). 

Later on they exhibit a spirit of opposition or jealousy, for while He is speaking to the people, His brethren, accompanied by His mother, sought Him, apparently to hinder His work (Matt. 12:46, 47;  Mark 3:31, 32;  Luke 8:19, 20).  In Mark 3:21 we read, "When His friends heard of it, they went out to lay hold on Him; for they said, He is beside Himself".  The expression "His friends" (margin "kinsmen") is hoi par autou, "those beside Him ", and it denotes a relationship so close as to identify them with the "brethren" of v. 31.  Again (John 7:3-10), they showed lack of sympathy with His work, and the reason is given in v. 5, "For neither did His brethren believe in Him". 

They are not seen again till, after His resurrection, they are gathered in the upper room with the apostles, and with His mother and theirs (Acts 1:14).  Their unbelief had gone.  James had become a servant to the Lord Jesus Christ (James 1:1), through the appearance to him of the risen Savior (1Cor. 15:7), and, shortly, is a "pillar" of the church in Jerusalem (Acts 12:17;  15:13-21;  21:18;  Gal. 1:19;  2:9, 12).  The other brethren seem to have joined in the witness by itinerating; see 1Cor. 9:5.

The natural meaning of the term "His brethren", in the Scripture record, would never have been challenged, but for the desire, when corruption crept into the churches (Acts 20:29, 30), of raising Mary from the position of "handmaid of the Lord" (Luke 1:38) to the exalted one of Theotokos, mother of God, whence it was an easy step to investing her with divine honors, as being herself a goddess.  And thus the way was cleared for identifying her with the great goddess of Paganism, who is the mother of a divine son, and who is yet a virgin, a deity best known by the appellation she bore in Egypt, Isis, the mother of Horus. 

So it was put forth that Mary had no children other than the Lord, and that His brethren and sisters were either the children of Joseph by a former wife, or the Lord's cousins, the children of Mary, the wife of Cleophas.  Those who maintained the former opinion asserted that Joseph was an old man when he married Mary.  Of this there is not the least hint in the Gospel records.  If he had older children, the right of the Lord Jesus to the throne of David would be invalidated, for the two genealogies in Matt. 1 and Luke 3 show that the regal rights were united in Joseph and Mary (Ap. 99).

With reference to Jerome's "cousin" theory, it may be stated that the word "brother" is used in Scripture, (1) in the sense of blood-relationship, as children of the same parent or parents; (2) in the wider sense of descent from a common ancestor, e.g. Acts 7:23, 25, where Abraham is the forefather; (3) in a still wider signification of fellow-man (Matt. 7:3-5;  18:15);   (4) to express spiritual relationship (Matt. 23:8;  28:10;  Acts 9:17;  Rom. 8:29;  Heb. 2:11).  In the passages where His brethren are referred to, viz. Matt. 12:46, 47;  13:55;  Mark 3:31;  Luke 8:19;  John 7:3, 5, 10;  Acts 1:14;  1Cor 9:5;  Gal. 1:19, only the first meaning can apply. 

Had they been cousins, the term would have been sungenes which is used in Mark 6:4;  Luke 1:36, 58;  2:44;  14:12;  21:16;  John 18:26;  Acts 10:24;  Rom. 9:3;  16:7, 11, 21, and  is translated "kin", "kinsman" or "kinsfolk", except in Luke 1:36, 58, where it is rendered "cousin".  The Scriptures distinguish "kinsman" from "brother";  see Luke 14:12;  21:16.  Only in Rom. 9:3 are the two words in apposition, and there "brother" is used in the sense of fellow-Israelite (No. 2).  "Brother", therefore, when used in N.T. in any sense other than that of No. 2 or of No. 3, must be restricted to signification No. 1.