To determine the necessity for maintenance dosages of prednisone in the management of heart transplant patients, a retrospective study was made of 86 patients undergoing orthotopic heart transplantation and two patients having heart-lung transplantation from June 1985 through October 1986. Group 1 (n = 52) had maintenance immunosuppressive therapy that included cyclosporine, azathioprine, and prednisone. Group 2 (n = 26) received only cyclosporine and azathioprine with no maintenance dosage of steroids. Data were analyzed for frequency of rejections, infections, noninfectious complications, and mortality. The rate of rejection was 1.44 episodes per patient in group 1 and 1.58 episodes per patient in group 2. Twenty of 52 patients (38%) in group 1 had no rejection compared with 12 of 36 patients (33%) in group 2 (p = not significant [NS]). One or more infections occurred in 30 patients (58%) in group 1, whereas only 12 patients (33%) in group 2 had infections (p < 0.05). Noninfectious complication rates were noted to be similar in both groups (27% versus 25%, p = not significant). There were five deaths in group 1: three from infections, one from rejection, and one from trauma. There were three deaths in group 2: two from infection and one from rejection. Although 14 patients in group 2 eventually were placed on low-dosage steroid maintenance, the remaining 22 patients (61%) never received maintenance dosages of steroids. We conclude that some patients can be successfully managed without maintenance dosages of steroids after heart transplantation. Such patients do not appear to have an increased risk of rejection and may have a reduced rate of infection. The long-term effect of eliminating maintenance dosages of steroids on the development of accelerated graft arteriosclerosis remains to be determined.