Cardiac symptoms, including hypotension, developed in three patients with advanced colorectal carcinoma while being treated with cisplatin (CDDP) and 5-fluorouracil (5-FU). In two patients, hypotension was associated with severe left ventricular dysfunction. All three patients required therapy discontinuation. Cardiac enzymes remained normal despite transient electrocardiographic (EKG) changes. The presentation and cardiac evaluation (hemodynamic, echocardiographic, and scintigraphic) of these patients suggest new manifestations of 5-FU cardiotoxicity that may be influenced by CDDP. The possible pathophysiologic mechanisms are discussed.