A multiple agent chemotherapy protocol utilizing cyclophosphamide, adriamycin, cytosine-arabinoside, vincristine, and prednisone (POACH) was administered to 65 patients with chronic lymphocytic leukemia. Nineteen (56%) of the 34 previously untreated patients responded, with (21%) of the patients obtaining a complete remission. The response rate for the 31 previously treated patients was significantly lower, with 2 complete remissions and 6 partial remissions. The median survival of the untreated patients was 58 months, compared with 15 months for the previously treated group (p less than 0.01). In both groups, patients who achieved a complete or partial remission had a significantly longer survival than did patients who did not respond. The response rates for all sites of involvement were similar. Sixteen (47%) of 34 previously untreated patients and 9 of 31 (29%) previously treated patients returned to Rai stage 0. The survival of patients who returned to stage 0 was significantly superior to that of others in both groups. The overall mortality during the study was significantly higher for previously treated patients. Pretreatment Rai stage was strongly predictive of death on study. Rai and Binet stages were not strongly predictive of response or length of survival in untreated patients but stages were predictive for survival and in treated patients. The regimen was well tolerated, with infectious complications being the major morbidity. Patients who responded to POACH had a significantly longer survival than did those who did not, and further attempts to improve the complete and partial remission rates in chronic lymphocytic leukemia will be undertaken.