Increased urinary excretion of immunoreactive thromboxane B2 (iTxB2) was found to have a high predictive value, with high sensitivity as an indicator of cardiac allograft rejection in both the immunosup-pressed and nonimmunosuppressed rat. In the animals receiving an allograft, urinary iTxB2 excretion significantly increased prior to the onset of rejection, remained elevated, and returned to basal values following completion of the episode. Urinary iTxB2 remained at baseline values in the control animals. The association between rejection and iTxB2 excretion was preserved regardless of the presence or nature of immunosuppression. Urinary iTxB2 excretion increased significantly prior to the reduction of graft beat or histological evidence of rejection. Evaluation of urinary iTxB2 monitoring as a noninvasive indicator for surveillance of clinical cardiac allograft rejection appears to be warranted.