To determine if repeated courses of high-dose prednisone given to patients with lymphoma as part of multiple-drug chemotherapy programs would lead to progressive adrenal suppression, serial cosyntropin stimulation tests were performed. Four patients with diffuse histiocytic lymphoma (group 1) received prednisone for 5 days every 3 weeks for five courses, and five patients with Hodgkin's disease (group 2) received prednisone for 14 days every 4 weeks for six courses. Testing was done on Day 1 of each treatment course prior to the administration of therapy and after the final course of chemotherapy. In group 1 patients, there was no evidence of adrenal suppression after any of the courses of prednisone. The plasma cortisol increments after cosyntropin injection were also normal. In the group 2 patients, significant depression of basal plasma cortisol concentrations was observed after the first and fifth courses of prednisone, compared to the pretreatment values. The depression reflected the previous course of prednisone administration only and was not progressive with subsequent courses. The plasma cortisol increments after cosyntropin injection were normal despite depressed basal plasma cortisol levels.