Postoperative nausea and vomiting after general anesthesia remains a complex and perturbing phenomenon associated with several factors. In women, the phase of the menstrual cycle as a factor in postoperative nausea and emesis is controversial. This retrospective study was performed to assess the effects of the menstrual cycle and efficacy of the antiemetic ondansetron on postoperative emesis. A total of 1169 ASA grade I-II patients from two double-blind, placebo-controlled studies were enrolled in 18 centers. Patients with irregular cycles or taking estrogens or progesterones were excluded from the analysis, leaving 873 patients eligible for this study. The patients were stratified on the basis of their last menses into four groups: 1) 1-8, 2) 9-16, 3) 17-28, and 4) 29-35 days. All patients received a general anesthetic with endotracheal intubation. Patients received either 1, 4, or 8 mg ondansetron or placebo given intravenously before induction of anesthesia. All patients were studied for a 24-h period. Emesis rates were compared with respect to the phase of the menstrual cycle and between menstruating and nonmenstruating patients. There was no relationship (P = 0.100) between the incidence of emesis and the phase of the menstrual cycle in the group receiving the placebo. There was, however, a significant reduction (P < 0.001) in emesis for the ondansetron-treated patients regardless of the phase of the menstrual cycle. In addition, ondansetron had a similar dose-response curve in both menstruating and nonmenstruating women.