ICRF-187 was given to 62 evaluable patients with advanced solid tumors in a Phase I clinical trial. Weekly infusions were given in dosages ranging from 0.85 g/m2 to 7.42 g/m2 for a total of four weeks with a two week rest period between courses. Dose-limiting hematological toxicity was seen in heavily pretreated patients at a dose of 3.8 g/m2/week. All patients also developed reversible SGOT elevations. In patients with less prior therapy hematologic toxicity was not dose-limiting but hepatotoxicity, manifest by transient SGOT levels greater than 5 times baseline was seen at 7.42 g/m2/week even though only 3/6 patients could receive 4 consecutive weekly doses. At virtually all dose levels tested some patients developed anemia. Other toxicities, including alopecia, nausea, vomiting and reversible serum amylase elevations, were mild. Cumulative monthly doses achieved on this weekly schedule are significantly higher than a 48-hour infusion or daily times 3 or 5 schedule in adults and a daily times 3 schedule in children. Pharmacokinetic studies in eight patients indicate that the drug disappears from the plasma biphasically with a terminal t1/2 of 3.2 +/- 0.9 hr. The total clearance was 288.7 +/- 85.0 ml/hr/kg and the volume of distribution (Vda) was 1.3 +/- 0.4 l/kg. Pharmacokinetics were not dose-dependent from 3.8-7.4 g/m2 and no difference in pharmacokinetics was found in patients studied during the first and second treatments of a course. If Phase II trials of ICRF-187 are to be pursued on this schedule, appropriate doses would be 3.8 g/m2/week X 4 for heavily pretreated and 7.42 g/m2/week for "good risk" patients. Because of erratic hematologic toxicity in heavily pretreated patients, some might only tolerate three weekly doses. In good risk patients transaminitis was significant but reversible, thus, Phase II protocols should include dose escalation schemata.