The pharmacokinetics and acute toxicity of carmustine (BCNU) have been studied in ten patients receiving high-dose combination chemotherapy with cyclophosphamide, cisplatin, and BCNU as treatment for advanced neoplasms. Patients received from 300 to 750 BCNU mg/m2 of body surface area as 2-hour infusion. The immediate effects of this schedule of BCNU included tachycardia, hypotension, flushing, confusion, nausea, and vomiting. Hypotension was a prominent feature of high-dose BCNU adminstration. The pharmacokinetics of high-dose BCNU were studied via serial blood samples obtained during and following BCNU infusion. Concentrations of BCNU in total plasma and ultrafiltrable (bioavailable) plasma were determined by high-pressure liquid chromatography with UV detection. Average pharmacokinetic parameters for bioavailable BCNU, calculated on the basis of a one-compartment model, include an elimination constant of 0.031 min-1 and a volume of distribution of 5.1 L/kg. Average clearance of total plasma BCNU is 77.6 ml/kg/min. When corrected to a constant dose of 1 g/m2, the average peak concentration at the end of the infusion was 7.8 .mu.M and the area under the curve was 538 .mu.M .cntdot. min. Plasma BCNU was largely (77%) protein bound. The distribution, clearance, and protein binding of high-dose BCNU were similar to those reported for standard-dose BCNU.