Histologically proved rejection after heart transplantation is commonly treated with intravenous steroids, 1 gm/day for 3 days. This regimen may result in severe side effects, however, both metabolic and infectious. In a total of 663 rejection episodes, we treated 397 with conventional steroid therapy, 1000 mg per day for 3 days (group 1), 199 with 500 mg/day for 3 days (group 2), and 67 with 250 mg/day for 3 days (group 3). Response to treatment was assessed by control biopsy after 1 week and graded as ongoing, resolving, or resolved rejection. The efficacy of the three regimens showed no significant differences between the groups as determined by the results of the subsequent biopsy. Ongoing rejection, resolving rejection, and resolved rejection, respectively: group 1-3.3%, 66.5%, 30.2%; group 2-8.0%, 66.8%, 25.2%; group 3-4.5%, 73.1%, 22.4%. We conclude that comparable effects, even with a considerable reduction of pulsed steroids, may be obtained in the treatment of cardiac allograft rejection, if triple-drug immunosuppression is used for maintenance therapy. It seems likely that steroid side effects may be decreased without jeopardizing the graft.