Although great strides have been made in clinical transplantation, infection remains a major problem. Critical to the understanding of the infectious disease problems of the present and the foreseeable future is the recognition that the risk of infection is largely related to the interaction of two factors: the net state of immunosuppression present and the epidemiologic exposures the individual patient encounters. It is now apparent that different immunosuppressive agents with comparable antirejection effects will have differing effects on infectious processes. This is perhaps best illustrated by comparing the effects of cyclosporin and antithymocyte globulin on a murine model of cytomegalovirus infection. Cyclosporin appears to have little ability to reactivate latent virus but has profound virus-promoting effects once replicating virus is present. In contrast, antithymocyte globulin has potent reactivating effects but little influence on replicating infection. Thus, the infectious disease problems observed will be affected by the timing, nature, dose, and duration of the various components of the immunosuppressive program. As far as epidemiologic exposures are concerned, there is increasing emphasis on nosocomial hazards, particularly those encountered at such common sites within the hospital as operating rooms and radiology suites. Viral infections remain the most important single infectious disease problem among transplant patients for the foreseeable future. Although immunoglobulin prophylaxis and ganciclovir therapy appear to hold promise for limiting the effects of cytomegalovirus infection, hepatitis virus infection remains a major issue. In addition, it is likely that HIV infection, particularly the clinical management of asymptomatic carriers of the virus, will have an increasing impact on clinical transplantation over the next decade.