Sixty consecutive previously untreated patients with non-Hodgkin's lymphomas (intermediate or high grade and/or bulky disease and/or presence of constitutional symptoms), were randomized to receive either CHOP-B or CEOP-B (31 and 29 patients, respectively) to compare the therapeutic activity and toxicity. Complete response was observed in 65% of the patients treated with CHOP-B and 62% with CEOP-B; relapse of the disease occurred, respectively, in 5/20 (25%) and 6/18 (33%) of CR. Relapse-free survival and overall survival at 5 yr resulted in both groups (RFS 68% and 62% and overall survival 62% and 62%, respectively). In addition, increasing the dosage of epirubicin did not result in an increase in the haematologic toxicity or percent of CR. The haematologic toxicity was slightly lower in CEOP-B. The cardiologic monitoring (Eco 2D and EKG-Holter) at 400 mg mq-1 of EDX and ADM did not demonstrate variations in cardiac function in the CEOP-B group, while in the ADM patients the ejection fraction was statistically lower as regards basal values. In conclusion, in our randomized study, substitution of ADM with EDX in non-Hodgkin's lymphomas in the CHOP-B regimen, did not decrease the therapeutic activity of the combined chemotherapy, while less toxicity (haematologic and cardiac) was observed. For these reasons, in our opinion, epirubicin can substitute adriamycin in second and third generation regimens for non-Hodgkin's lymphomas in which the major drawback for a wider diffusion is the severe toxicity observed.