Two of the most consistent correlates of sexual orientation in men are handedness and fraternal birth order (i.e., number of older brothers). In the present study, the relationship among handedness, older brothers, and sexual orientation was studied in 4 samples of heterosexual and gay or bisexual men (N = 944). Unlike previous studies, which have only observed an increased rate of non-right-handedness in gay or bisexual men relative to heterosexual men, an elevated rate of extreme right-handedness was found in gay or bisexual men relative to heterosexual men. The results also demonstrated that older brothers moderate the relationship between handedness and sexual orientation. Specifically, older brothers increase the odds of being gay or bisexual in moderate right-handers only; in both non-right-handers and extreme right-handers, older brothers do not affect (or decrease) the odds of being gay or bisexual. The results have implications for an early neurodevelopmental origin to sexual orientation in men.