Ten patients with malignant pericardial effusion were treated with intrapericardial injection of OK-432 (penicillin-treated and heat-treated lyophilized powder of the substrain of Streptococcus pyogenes A3). After intrapericardial insertion of a catheter, a maximal volume of pericardial fluid was withdrawn with cytologic confirmation of malignancy. Five or 10 Klinische Einheit (KE) (KE is a unit used to express the strength of a preparation) of OK-432 diluted in 20 ml of saline was injected into the pericardial space in seven and three patients, respectively. It was repeated in case of reaccumulation. Seven patients were treated only once and the remaining three required a second treatment. Complete control of pericardial effusion was achieved in all patients for an average of 329 days (range, 54 to 790 days). Fever and chest pain were experienced in six and five patients, respectively, but were controlled with antipyretics. Two of three patients who received 10 KE of OK-432 experienced hypotension that was successfully controlled with vasopressor drugs with or without reaspiration of pericardial fluid. Rapid reactive reaccumulation of the pericardial fluid was thought to be a cause of hypotension. A follow-up computed tomography (CT) scan was performed in seven patients and a thickened pericardium was noticed in five; no patients had constrictive pericarditis. These results suggest that intrapericardial administration of 5 KE of OK-432 is an effective and safe treatment for malignant pericardial effusion.