Adult, regularly cycling female Fischer rats were injected daily with 10 mg/kg fluoxetine for 12-23 days. In the first experiment, body weight and vaginal smears were monitored daily. Fluoxetine treatment reduced body weight within the first 24 h of treatment. Fluoxetine treatment also elongated the estrous cycle, reduced blood levels of progesterone, and eliminated lordosis behavior. In the second experiment, body weight and food intake were examined and a pair-fed group was included to determine if fluoxetine-induced anorexia contributed to the disturbance of the estrous cycle. In pair-fed rats, effects similar to fluoxetine treatment were present. These results lead to the suggestion that fluoxetine's anorectic properties could disrupt the female's normal endocrine cyclicity and that this disruption could be relevant to the reduction in sexual behavior and motivation. However, when the duration of fluoxetine treatment was extended beyond 16 to 17 days, fluoxetine-treated female rats reinitiated vaginal cyclicity and showed evidence of normal sexual receptivity. In contrast, the estrous cycles of their pair-fed counterparts remained disrupted. Thus, restricted food intake appears to contribute to the disruption of the estrous cycle and elimination of sexual receptivity during fluoxetine treatment. However, compensatory changes in the serotonergic system that are associated with chronic fluoxetine administration may contribute to the gradual recovery of estrous cyclicity and sexual receptivity of the fluoxetine-treated animals.