Intercellular adhesion molecule-1 (ICAM-1) is induced on allograft cells in association with acute rejection and plays important roles in the rejection process. Mice with abdominal heart transplants were studied to determine whether an increase in ICAM-1 expression in rejecting cardiac allografts could be detected by radioimmunoscintigraphy. Allografts from BALB/c donors were transplanted into C3H/He recipients (n = 7). Two of the allografted mice were treated with FK506 (2 mg/kg/day) and four isografted C3H/He mice served as controls. One to eight days after transplantation each mouse was injected intravenously with 50 microCi of 123I-labeled anti-ICAM-1 monoclonal antibody (YN1/1.7). After imaging the mice were killed for tissue counting and histopathology. Graft to native heart radiotracer uptake ratio in the mice with rejecting cardiac allograft (2.12 +/- 0.22, n = 5) was significantly greater than that in the mice with non-rejecting graft (1.23 +/- 0.14, n = 6, p < 0.001). In contrast to non-rejecting grafts, a rejecting allograft with lymphocyte infiltration but without myocyte necrosis and other allografts with relatively advanced rejection could be identified by the scintigraphy. We conclude that 123I-labeled anti-ICAM-1 antibody imaging is a noninvasive method for detecting cardiac allograft rejection.