Meta-analysis of aggregate data from 14 samples representing 10,143 male subjects shows that homosexuality in human males is predicted by higher numbers of older brothers, but not by higher numbers of older sisters, younger brothers, or younger sisters. The relation between number of older brothers and sexual orientation holds only for males. This phenomenon has therefore been called the fraternal birth order effect. Research on birth order, birth weight, and sexual orientation suggests that the developmental pathway to homosexuality initiated by older brothers operates during prenatal life. Calculations assuming a causal relation between older brothers and sexual orientation have estimated the proportion of homosexual men who owe their sexual orientation to fraternal birth order at 15% in one study and 29% in another. The maternal immune hypothesis proposes that the fraternal birth order effect reflects the progressive immunization of some mothers to male-specific antigens by each succeeding male fetus and the increasing effects of such immunization on sexual differentiation of the brain in each succeeding male fetus. There are at least three possible mechanisms by which the mother's immune response could influence the fetus: the transfer of anti-male antibodies across the placenta from the maternal into the fetal compartment, the transfer of maternal cytokines across the placenta, and maternal immune reactions affecting the placenta itself. This hypothesis is consistent with recent studies showing that the quantity of fetal cells that enter the maternal circulation is greater than previously thought, and that the number of male-specific proteins encoded by Y-chromosome genes is greater than previously thought.