B-type natriuretic peptide (BNP) concentrations, a cardiac hormone released upon cardiac stress, was monitored in patients after heart transplantation. Rejection was assessed by the International Society for Heart and Lung Transplantation (ISHLT) criteria. BNP was assessed by a cross-sectional approach. We found significantly (p = 0.024) increased concentrations during rejection episodes of ISHLT grade 2 and higher. BNP yielded only a moderate diagnostic accuracy (area under the receiving characteristic curve: mean = 0.76, 95% confidence interval 0.53-0.92) to detect clinically significant episodes of rejection, which was too low to replace endomyocardial biopsies. Acute rejection episodes were associated with marked BNP increases and a significant decrease in case of successful treatment in the individual long-term monitoring in the majority of patients. BNP monitoring seems to be a useful addition in the individual follow-up of heart transplant recipients to rule out significant rejection.