Twenty-six patients being treated with 5-fluorouracil-adriamycin-cyclophosphamide (FAC), or vincristine-adriamycin-cyclophosphamide (VAC) chemotherapy completed a randomized, double-blind, cross-over study in which the antiemetic activity of thiethylperazine (6.5 mg p.o. every 8 h X 5 days) was compared with that of the combination of thiethylperazine (same dosage) plus amitriptyline (25 mg p.o. every 8 h X 5 days). This combination was designed to obtain a simultaneous blockade of the dopamine D-2, histamine H-1, and muscarinic cholinergic receptors of the central structures responsible for emesis (chemoreceptor trigger zone and vomiting center). The combination significantly decreased both the number of emetic episodes (P less than 0.05) and the duration of emesis (P less than 0.01) compared with thiethylperazine alone. The combination was also preferred by a significantly higher number of the patients (P less than 0.001) who were exposed to both the types of antiemetic treatment under trial. The combination of thiethylperazine plus amitriptyline was shown to have a satisfactory antiemetic activity against vomiting induced by VAC chemotherapy in males; it afforded major protection (two emetic episodes or fewer) in 83% of the cases. Nonetheless, it cannot be considered a satisfactory treatment for the control of vomiting induced by FAC chemotherapy in female patients, only 43% of whom achieved major antiemetic protection.