A randomized controlled study was performed to evaluate the efficacy of intrapleural and systemic administration of OK-432, streptococcus preparation, in patients with cancerous pleurisy. A total of 53 patients were accessed to the study: 29 patients for the OK-432 group and 24 patients for the control group. Intrapleural instillation of 50 mg of adriamycin and a combination chemotherapy of MFC (mitomycin C 0.08 mg/kg, 5-FU 10 mg/kg, ara-C 0.8 mg/kg iv, weekly) were administered in both groups. In the OK-432 group intrapleural instillation of 2 units of OK-432 was administered daily until disappearance of pleural effusion; thereafter, 2 to 5 units of OK-432 were administered intradermally every other day. Patients with stage III in the OK-432 group survived significantly longer than those in the control group (P less than 0.05), but there was no significance between in patients with stage IV of both treatment groups. Also patients with PPD negative skin reaction at the time of beginning of treatment in the OK-432 group survived significantly longer than those in the control group (P less than 0.001), but there was no significance between both treatment groups in patients with PPD positive skin reaction at the time of beginning of treatment. Eighteen (62%) of 29 patients treated with OK-432 had a fever, but well tolerated.