Forty-five patients received escalating dose rates of continuous infusion thio-triethylene thiophosphoramide (TEPA) for either five (26 patients) or 28 (19 patients) days. Dose rate limiting toxicity for the 5-day infusion was myelosuppression with leukocyte and platelet nadirs on days 21 and 28, respectively. The nadir was influenced by the presence and degree of liver disease. The optimal dose rate for 5-day infusion in the absence of liver disease was 12 mg/m2/d and was reduced to 8 mg/m2/d in patients with major liver disease. Dose rate limiting toxicity for the protracted 28-day infusion was leukopenia. The optimal dose rate for the 28-day infusion was 4 mg/m2/d. Pharmacologic studies included determination of plasma steady state concentrations (CSS) of thio-TEPA and TEPA. Dose rates up to 10 mg/m2/d produced thio-TEPA and TEPA CSS below the levels of detection of available analytical methodology, except in three patients infused at dose rates of 1, 2, and 4 mg/m2/d, respectively.