From March 1984 to June 1987, 51 patients underwent primary orthotopic heart transplantation at the Second University Department of Surgery, Vienna. Recipients were immunosuppressed with a combination of either ciclosporine and azathioprin (double drug regimen = DD, 10 patients), or ciclosporine, azathioprin and low-dose steroids (triple drug regimen = TD, 33 patients). Four patients who died intra- or perioperatively and 4 who were switched to conventional therapy were excluded from analysis. In both groups, ciclosporine was administered to obtain whole blood HPLC trough levels of 200-400 ng/ml in the 1st month, 150-250 ng/ml from the 2nd to the 6th and 100-150 ng/ml after the 6th month. Azathioprin 2 mg/kg per day was given, and in TD patients, an additional 0.2 mg/kg per day of prednisolon: all patients received prophylactic antithymocyte globulin for 7-10 days postoperatively. Five deaths from acute rejection in the DD group contrasted with none in the TD group. The high incidence of fatal rejection episodes was reflected in a 40% Kaplan-Meier 1-year survival for DD vs 84% for TD (p less than 0.0001). Analysis of endomyocardial biopsies (DD vs TD) demonstrated 20.4% vs 57.0% absent, 46.0% vs 29.5% mild, 31.2% vs 12.4% moderate and 2.4% vs 1.1% severe rejection. Fatal and nonfatal infections and toxic side effects occurred with the same frequency in both protocols. Calculation of mean ciclosporine levels resulted in 249.7 ng/ml (TD) and 206.0 ng/ml (DD) in the 1st month (p less than 0.05). Consequently, adjunctive maintenance low-dose steroids combined with increased ciclosporine levels in the early posttransplant course are considered responsible for the improved results.