Fifty patients undergoing orthotopic cardiac transplantation were monitored over 34 months for evidence of infection. Four separate immunosuppressive protocols were used during the course of the study; the most recent protocol (protocol 4) employed significantly lower overall steroid dosages than the earlier protocols (protocols 1,2, and 3). All immunosuppressive regimens used cyclosporine, and azathioprine was added in the last three protocols. Statistical techniques to compare the occurrence of infection in protocols 1,2, and 3 v protocol 4 showed that patients in protocol group 4 (n = 21) had significantly more time free of pneumonia (P = .02) and major infections (P = .04) and marginally more time free of symptomatic cytomegalovirus infection (P = .08) than patients in protocol groups 1, 2, and 3 (n = 29). The median incidence of major infection per month was lower for protocol group 4 (P = .02). The time free of viral infection did not differ significantly between the two groups (P = .75) nor did the median incidence of rejection per month (P = .19). The authors conclude that reduction of steroid dosages in cardiac transplant patients receiving cyclosporine is associated with a significant decrease in the incidence of clinically important infections.