A liposome-encapsulated form of doxorubicin (TLC D-99), which was shown in preclinical toxicology to be less toxic to the gastrointestinal tract and myocardium than free doxorubicin, was administered by constant infusion (1.00-1.80 h) to 38 patients in single doses of 20, 30, 45, 60, 75, and 90 mg/m2 every 3 weeks and daily for 3 days at doses of 20, 25, and 30 mg/m2/day. The dose-limiting toxicity was leucopenia: the maximum tolerated doses were one at 90 mg/m2 and three at 25 mg/m2/day. Nausea, vomiting, and stomatitis were minimal or absent at each dose; alopecia was minor. Fever and chills were noted at most of the doses, and malaise was seen in some patients, especially at the higher doses. No hepatic, renal, or other organ toxicities were observed. Clinical cardiac toxicity was not observed in any patient; however, the cumulative doxorubicin dose was greater than 400 mg/m2 in only one patient. There was large variation among patients in estimated pharmacokinetic parameters and profiles. Higher plasma levels and dose intensities were achieved with TLC D-99 than were predicted for free doxorubicin. Liposome-encapsulated doxorubicin was well tolerated and produced less nausea, vomiting, and stomatitis than would be expected with free doxorubicin administered at equally myelosuppressive doses.