The vast majority of studies on circadian rhythms in rodents use male animals only. Sex differences in baseline locomotor activity patterns are thought to be limited to small changes in activity onset as a function of estrous cycle phase, but we hypothesized that more differences would be revealed if the circadian system were challenged. Therefore, we performed a series of studies comparing responses of the circadian clock in male and females in Syrian hamsters and mice (C57BL/6J strain). Hamsters show a high-amplitude 4-day cycle of wheel-running activity that is estrous-cycle dependent in females, while this variability is not apparent in female mice. In hamsters, females took significantly longer to reentrain to a 7-hour delay of the light/dark cycle than males, despite there being no difference between males and females in the phase shifting responses to 15-minute light pulses. Injection of the 5-HT_1A,7 agonist 8-OH-DPAT resulted in phase advances that did not differ between male and female hamsters, but females showed a one-day delay of the estrous cycle if the circadian phase shift was greater than one hour. Mice were not examined with 8-OH-DPAT as they do not show large phase advances in response to injection. However, mice did show a sex difference in food anticipatory activity when placed on a daily schedule of restricted feeding (four hours only during the light phase), with females showing significantly reduced food anticipatory activity as compared to males. This food anticipatory activity is thought to result from the function of a food entrainable circadian oscillator distinct from the one that drives diurnal/nocturnal activity patterns. We suggest that both central and peripheral circadian clocks may show sex differences in function that are only revealed during disruptive challenges.