4'-Carboxyphthalato(1,2-diaminocyclohexane)platinum(II) is a new, second generation platinum analog which had demonstrated in vitro activity in L1210 cell lines resistant to cisplatin and had less nephrotoxicity than did cisplatin in preclinical animal testing. A Phase I trial with this agent has been performed in 45 patients with advanced refractory cancers. Nine dosage levels, ranging from 40 to 800 mg/sq m, were studied. Major toxicities seen were myelosuppression, nephrotoxicity (which was generally mild), nausea and vomiting (which was quantitatively less than that seen with cis-platin), allergic reactions, and a peripheral neuropathy. The dose-limiting toxicity was thrombocytopenia. Pharmacokinetics performed at three dosage levels indicates that 4'-carboxyphthalato-(1,2-diaminocyclohexane)platinum(II) has a long t1/2 of 20 to 30 hr (total platinum) and is only partially excreted in the urine and that a high proportion of the drug is nonfilterable within 30 to 60 min of administration. Therapeutic responses were seen in nasopharyngeal carcinoma, adenocarcinoma of the cervix, and lung and gastric cancer. As a starting dose for Phase II studies, which are planned for patients with ovarian, testicular, lung, gastric, and esophageal cancers, 640 mg/sq m given every 3 to 4 weeks is recommended.