The aim of this paper was to describe striking gender differences observed between emesis and hiccups in patients receiving cisplatin-based chemotherapy (CT) and one of two dexamethasone-containing anti-emetic regimens. Four hundred patients were evaluated in a crossover study with two arms. Patients in arm A received three doses of ondansetron 8 mg i.v. at 4-h intervals plus dexamethasone 20 mg i.v. from the start of CT, followed by dexamethasone 5 mg i.v. every 12 h, until CT was complete, after which dexamethasone was discontinued. For patients in arm B the treatment was the same as in arm A except that the three doses of ondansetron 8 mg i.v. were given at 24-h intervals. There were 363 patients in arm A and 358 patients in arm B. Vomiting/nausea/hiccups were observed in 30.3%/41.6%/23.7% of patients in arm A and 28.8%/39.1%/23.7% of patients in arm B, respectively. Comparison showed that the rates for complete control of vomiting and nausea on days 1 through 6 were significantly lower in women (P<0.0001 and =0.0004 in arm A and P<0.0001 and <0.0001 in arm B, respectively). Men had a significantly higher incidence of hiccups (P<0.0001 in both arms), but no apparent associations with age, cisplatin dose, tumor type, and the presence of vomiting and nausea during CT were found. Hiccups usually began 24 h after cisplatin administration and persisted for some days. Women had significantly higher rates of vomiting and nausea. The cause of the gender discrepancy is unknown.