Tc-99m pyrophosphate (PPi) uptake has been measured in a rat model of heterotopic heart transplant at 5 days after transplantation. Comparison of tracer uptake, as a ratio between the heterotopic transplanted heart and the recipient's native heart, was made in four groups of animals. Group 1, with transplants between animals of isogeneic strain showed a lower ratio, significantly different from the ratio in Group 2 in which transplants were between nonisogeneic animals. The ratio of uptake after transplantation between nonisogeneic animals treated with 10 mg/kg-day of cyclosporine (Group 3), was not significantly different from Group 1. In contrast, the ratio of uptake between nonisogeneic animals treated with sub-therapeutic doses of cyclosporine (Group 4), was not significantly different from Group 2. In groups 1, 2, and 3 there was a correlation between the histology of the transplanted hearts, graded 1 to 5 according to the severity of rejection, compared with the uptake of Tc-99m PPi. This agent can therefore be used to diagnose cardiac rejection in a rat model, and the results correlate well with the severity of rejection as assessed histologically.