Deoxyspergualin (DSG) is an analog of the polyamine spergualin with preclinical evidence of activity in murine and human tumor models. This phase I study examined a 120 h continuous infusion schedule in 56 patients with refractory solid tumors at doses ranging from 80 to 2792 mg/m2/day. Dose-limiting toxicity was reversible hypotension and appeared to be associated with plasma levels of DSG > 4 micrograms/ml. Other dose-dependent effects noted were pruritus and circumoral paresthesias. Myelosuppression and gastrointestinal toxicities were mild and sporadic. Two patients with refractory head and neck cancer had minor responses. The recommended phase II dose on this schedule is 1800 mg/m2. Additional monitoring to identify immunologic properties included immunophenotyping of peripheral lymphocytes and cytotoxic activity by means of standard 51Cr-release assays. These studies revealed a non-dose-dependent increase in the number of cells expressing T cell antigens predominantly the T suppressor (CD8) phenotype posttreatment. In three patients, a mild increase in LAK activity was noted post-treatment without a consistent relationship to dose or change in cell surface antigens. Pharmacokinetic studies were completed on 26 patients ranging from doses of 80 to 2792 mg/m2. The average plasma concentration ranged from 0.07 to 7 micrograms/ml. DSG was rapidly cleared from the plasma with a mean terminal half-life of 1.9 h. Mean total body clearance was 25.24 l/h/m2. Further in vivo immunologic studies should be pursued while the agent is studied in fixed dosage phase II clinical trials.