Esorubicin (4' deoxydoxorubicin) is a new analogue of the anthracycline, doxorubicin. This compound lacks the hydroxyl group at 4' position on the amino sugar of the anthracycline. Phase II study was designed to determine the clinical response rate and to define the qualitative and quantitative toxicities of esorubicin in patients with adenocarcinoma of the pancreas. Fifty-eight patients with inoperable adenocarcinoma of the pancreas were entered on the study, 47 were evaluable for response, and 57 were evaluable for toxicity. The dose of esorubicin was 30 mg/m2 for good risk patients and 25 mg/m2 for poor risk patients every 21 days and administered IV push through a side arm of a running IV. Diphenhydramine, 50 mg is administered IM prior to the administration of the drug to block local venous reaction. Subsequent doses of esorubicin were modified according to granulocyte and platelet nadirs and the drug was not administered until recovery of platelets (greater than 100,000/microliters) and wbc (greater than 3000/microliters). Three partial responses, 20 stable, and 31 with increased disease were observed. Forty-seven had severe granulocytopenia (less than 250), and two patients had severe thrombocytopenia (less than 25,000). One patient experienced a decrease in left ventricular ejection fraction with a total dose of 180 mg/m2. The dose of esorubicin in this study demonstrated that the drug has minimal activity in adenocarcinoma of the pancreas but the toxicity is tolerable. Search should continue for single agents with activity in this disease.