The most common cardiotoxic effects of 5-fluorouracil (5-FU) are chest pain and ischemic ECG abnormalities. Coronary vasospasm may be the underlying mechanism. If so, prophylactic treatment with calcium channel blockers might have a beneficial effect. In the present study, prophylaxis with verapamil (120 mg three times daily) was given to 58 patients with esophageal or advanced head and neck carcinoma during induction chemotherapy with cisplatin and continuous infusion with 5-FU. Signs of ischemia appeared in 12% of the patients as compared to 13% in a previously studied compatible group of patients not receiving prophylaxis. The study does not support the hypothesis that prophylactic treatment with verapamil reduces the incidence of ischemia in patients undergoing 5-FU treatment. Verapamil might, however, modify the adverse cardiac effects of 5-FU by preventing supraventricular tachyarrhythmia.