The development of clinically useful drugs is a priority of clinical cancer research. CI-973, [SP-4-3(R)]-[1,1-cyclobutanedicarboxylato(2-)](2-methyl-1,4- butanediamine-N,N1) platinum, has been shown in preclinical murine and human tumor models to have activity equivalent or superior to that of cisplatin and carboplatin and to exert activity against cisplatin-resistant cell lines. In addition, preclinical testing suggests a reduced toxicity profile for CI-973 as compared with currently available drugs, especially decreased nephrotoxicity, ototoxicity, and gastrointestinal toxicity. A total of 29 (28 evaluable) patients with solid tumors were treated with intravenous CI-973 given over 30 min every 4 weeks. No routine pre- or post-treatment hydration or antiemetic program was used. The CI-973 doses given were 75, 150, 170, 188, 230, and 290 mg/m2. The dose-limiting toxicity was granulocytopenia. Nausea and vomiting occurred in the majority of patients but was mild to moderate in severity. No renal or auditory toxicity was seen. The maximum tolerated dose (MTD) for patients who had a good performance status, had not received prior radiation therapy to bone marrow, and had not previously been exposed to platinum or stem-cell toxin was 290 mg/m2. For those who had received prior radiation therapy, had a performance status of 2 or worse, or had previously been exposed to platinum or stem-cell toxin, the MTD was 230 mg/m2. The recommended phase II starting doses for these groups of patients are 230 and 190 mg/m2, respectively. No clinical tumor response was seen in this phase I study.