Neocarzinostatin (NCS) is an acidic protein with proven antitumor activity in experimental animals and it is now undergoing clinical trials as a cancer chemotherapeutic agent. In the pharmacokinetic analysis of NCS in rabbits, the agent was distributed at high concentration in the lungs. So NCS was administered in advanced lung cancer. Fourteen patients, 9 with squamous cell carcinoma, 5 with adenocarcinoma, were treated with 0.12 mg/kg/day by drip infusion for 5 consecutive days. Courses were repeated at 3-week intervals if allowed by bone marrow recovery. Total doses ranged from 15 to 200 mg, and one patient with squamous cell carcinoma was induced into a good Partial Response. Dose-limiting toxicity was myelosupression, anemia in 7 patients, leucocytopenia in 10 patients and thrombocytopenia in 7 patients. Myelosupression was more pronounced in patients who had received more than 100 mg of NCS. Nadir of leucocyte and thrombocyte decreased with each course. Other toxicities of NCS included anorexia, vomiting and fever. The pharmacokinetics of NCS after i.v. injection were examined in patients with lung cancer with pleural effusion. The concentration of NCS in blood decayed rapidly as a diexponential function with time. NCS was rapidly excreted in the urine, and high concentrations of NCS were detected in pleural effusions.