It was recently discovered that the human right-versus-left-hand use preference and the direction of scalp hair-whorl rotation develop from a common genetic mechanism. Such a mechanism controls functional specialization of brain hemispheres. Whether the same mechanism specifying mental makeup influences sexual preference was determined here by comparing hair-whorl rotation in groups enriched with homosexual men with that in males at large. Only a minority of 8.2% (n = 207) unselected ‘control’ group of males had counterclockwise rotation. In contrast, all three samples enriched with homosexual men exhibited highly significant (P < 0.0001), 3.6-fold excess (29.8%, n = 272) counterclockwise rotation. These results suggest that sexual preference may be influenced in a significant proportion of homosexual men by a biological/genetic factor that also controls direction of hair-whorl rotation.