In a prospective, multicenter study, we evaluated the incidence of adverse cardiac effects in 1097 patients receiving 5-FU as a short i.v. perfusion or as a continuous perfusion over 3 to 5 days. There were 29 cardiac events (incidence 1.6%; 4.5% in patients with a history of cardiovascular disease, 1.1% in the remainder). Adverse effects were more frequent in the patients with advanced WHO (WHO = OMS) stage (2 or 3) primary tumors of the upper respiratory or digestive tract, or of the gastrointestinal tract, when 5-FU was given as a continuous perfusion. They also appeared to be more frequent in patients with a history of cardiovascular disease, and mainly occurred during the second or third day of the first course of treatment. Retreatment of eight patients with 5-FU led to the recurrence of symptoms in five. The outcome of these adverse cardiac effects was generally favorable, but 11.5% of the patients died.