Sexually satiated male hamsters preferred to investigate and to mount an anesthetized, estrous, novel female over a similarly presented female with which the male had become satiated (the Coolidge effect); likewise, such males preferred a novel female recently mated with another male over the familiar female but showed no preference between fresh and mated novel females. Thus the Coolidge effect is at least partly dependent on discrimination of a new female by chemical cues. Another experiment indicated that transfer of a male's own scent during mating is not involved in discrimination between familiar and novel females. Flank gland secretion of females were sufficient for individual discrimination by males, whereas head region scents and vaginal secretions were not sufficient. The presence of female's flank glands was not, however, necessary for such discrimination. Lesions of or removal of the vomeronasal organ did not disrupt the preferences of sexually satiated males for a novel female, but elimination of main olfactory system function by ZnSO4 treatment of the olfactory mucosa did abolish such preferences. Thus olfactory cues are sufficient for individual discrimination of novel females by sexually satiated male hamsters, and such recognition leads to increased sexual arousal. These processes are mediated by the main olfactory system but not the vomeronasal accessory-olfactory system.