The results of a prospective trial with a specifically devised chemotherapy regimen in elderly patients with unfavorable non-Hodgkin's lymphoma (NHL) are reported. Between April 1983 and April 1986, 37 consecutive patients 70 years old or more (median age 80) received etoposide and prednimustine (E + P) 100 mg/m2 p.o. for 5 days every 21 days. Thirteen patients were previously treated. Objective response rate in the 35 evaluable patients is 66% with 46% complete response. The objective response rate in the 22 previously untreated patients is nearly 70% with 50% complete response. Median survival is 14 months. The overall toxicity was reasonably acceptable. There were 5% (2 patients) treatment-related deaths, but in an unselected elderly population. We experienced the usefulness of a properly oriented clinical approach to elderly patients with NHL. We suggest that a combination regimen E + P, suitable for oral administration, may be safely employed in elderly patients with unfavorable NHL.