4'-Deoxydoxorubicin (dxDx), a new doxorubicin analogue, was administered intravenously on a 3-week schedule to 73 patients affected by advanced malignant neoplasms. Sixty-five patients, treated with eight dose levels ranging from 10 to 45 mg/m2, were evaluable. The dose-limiting toxicity was myelosuppression, mainly leukopenia. About one third of the patients complained of vomiting which was almost always mild. Minimal hair loss was also documented in about 40% of patients. No hepatic or renal toxicity was observed. Transient and aspecific electrocardiographic changes were recorded in 6% of patients after 1 h and in 3% after 24 h from drug injection. Left ventricular ejection fraction was decreased in two patients after a cumulative dose of 90 mg/m2. One patient died with cardiorespiratory insufficiency and his initial cardiovascular disease might have been aggravated by dxDx. No changes in myocardial function parameters were documented in 18 patients who reached higher cumulative doses, i.e. greater than or equal to 100 mg/m2 and greater than or equal to 200 mg/m2. The highest total dose administered in this study was 340 mg/m2. Therapeutic activity was observed with doses ranging from 25 to 45 mg/m2. Partial response was documented in pancreatic, colon, anal and breast carcinomas as well as in non-Hodgkin's lymphoma. Minor response was observed in prostatic, thyroid, and renal carcinomas as well as in chronic lymphocytic leukemia. The maximum tolerated dose was assessed to be between 40 and 45 mg/m2. A Phase II trial is ongoing utilizing the dose of 35 mg/m2 every 3 weeks.