The effectiveness of combination chemo-immunotherapy with ADM, CPA, FT-207 plus OK-432 for advanced and/or recurrent carcinoma of the breast was investigated in a prospective randomized and controlled study. Fifty-seven patients from 10 major hospitals in the Tohoku area were grouped into the following protocols: protocol I (ADM 40-60 mg/body on the first day, CPA 150mg p.o./body/from the 5th to the 9th day, FT-207 600mg p.o./body/from the 10th to the 30th day, OK-432 total dose 30KE and over) and protocol II(ADM, CPA, FT-207). These protocols were performed repeatedly two or more times. Forty-five cases from the total of 57 were available for this randomized study. Twenty-three of these cases were treated with protocol I (OK-432 group), while the remaining 22 were treated with protocol II (non-OK-432 group). The OK-432 group and the non-OK-432 group were compared for prognostic factors, and no difference could be observed between the two groups. Seven cases from each group were interpreted as effective clinically by Koyama-Saito's criteria of PR or better. Eight cases from the OK-432 group and 4 from the non-OK-432 group were interpreted as effective by Karnofsky's criteria of I-A and better, but no statistical difference was recognized between the two groups. The survival curve obtained by the Cox-Mantel test for the OK-432 group was better than that for the non-OK-432 group (U = 1.943, p less than 0.1).