The sera of 20 random human heart transplant recipients, drawn before the administration of immunosuppressive medications, were screened for the presence of factors that might inhibit the mixed lymphocyte reaction. The donors for the lymphocyte cultures were unrelated both to one another and to the heart donor and recipient. Inhibition was defined as a reduction of the number of transformed cells produced in vitro to less than one third of that produced in autologous serum. It appears that patients who have had previous heart surgery on bypass fare better with heart transplants than those who have not had surgery. This may indicate some change in the overall physiology of the former class of patients resulting in better acceptance of the transplant. In turn, this could be due to the development of a serum factor or an impairment in the patients' cellular immune systems. In the series of recipients studied, the majority possessed serum inhibitory factors possibly non specific by products of their heart failure. The precise nature of these factors has yet to be determined. Future research is planned to determine whether bypass surgery is responsible for the stimulation of new immuno depressive factors or if in some way it boosts the titer of preexisting factors.