We started a treatment trial for malignant pericardial tamponade with intracavitary oxytetracycline, 500-1,000 mg/day, administered via an indwelling pericardial cannula after extraction of as much pericardial fluid as possible. This procedure was repeated every 24 h for 6 consecutive days or until no more fluid could be drained. Eleven consecutive patients were entered in the study. The responses were obtained by clinical examination, chest roentgenogram and echocardiogram, prior to and after treatment. The primary cancer was located in the breast in 7 patients, in the stomach in 2 patients, and in the lung in 2 patients. In all cases, systemic chemotherapy or hormonal therapy was started after the pericardial tamponade was cured. The mean tetracycline dose per patient was 3,000 mg (range 1,500-6,000). All patients responded to the treatment with rapidly improving symptoms. Response persisted during a median of 9 months coinciding roughly with the median survival because all patients died because of progression of the neoplasm at sites other than the pericardium with no evidence of pericardial relapse. The main concomitant effects were mild local pain during tetracycline instillation in 4 patients, and transient fever (less than 39 degrees C) in 3. These data suggest that intracavitary oxytetracycline is perhaps less toxic and similar by successful as tetracycline hydrochloride in malignant pericardial tamponade.