Twenty-one patients with nonresectable hepatocellular carcinoma (HCC) received intraarterial infusion chemotherapy of Adriamycin (Adria Laboratories, Columbus, Ohio) via an indwelling catheter in the hepatic artery. Additional intratumoral injection therapy of OK-432 (50 KE) was administered to ten of these 21 patients. Nine of the ten patients showed a remarkable decrease in lymphocyte count on the first day after therapy. In all of the patients with a decreased lymphocyte count, computed tomograms (CTs) demonstrated evidence of necrosis associated with a rapid decrease in alpha fetoprotein (alpha-FP). Blastogenesis of lymphocytes in peripheral blood induced by phytohemagglutinin (PHA) increased by 3.99 +/- 1.9 (mean +/- SE) times 4 weeks after therapy. On the basis of these results, we concluded that intratumoral injection therapy of OK-432 apparently produced initiation of necrosis in HCC by cell-damaging activity as well as by improvement of cell-mediated immunity.