Thirty-three unselected patients with cardiac tamponade secondary to malignant pericardial effusion were treated by intrapericardial instillation of tetracycline hydrochloride. Complete control of the initial signs and symptoms of tamponade was obtained in 30 patients without concomitant chemotherapy or radiotherapy. The procedure did not result in clinically significant complications. Failure of the technique was related to premature removal of the catheter by the patient (one patient) or the inability to totally remove hemorrhagic, clot-filled pericardial fluid (two patients). Survival ranged between 28-704 days and extended survival was related to the performance status and/or chemoradiosensitivity of the primary cancer. No patient successfully treated subsequently developed recurrent cardiac tamponade or alternatively, constrictive pericarditis. Tetracycline pericardial instillation remains a safe, simple, and efficacious treatment of tamponade secondary to malignant disease.