The capability of radionuclide imaging to detect experimental aortic valve infective endocarditis was assessed with indium-111 ((111)In)-labelled blood cells. Sequential cardiac imaging and tissue distribution studies were obtained in 17 rabbits with infective endocarditis after administration of (111)In-platelets and in five after (111)In-polymorphonuclear leukocytes. Forty-eight to 72 hours after platelet administration, in vivo imaging demonstrated abnormal (111)In-uptake in all animals in the region of the aortic valve in an anatomically distinct pattern. Images of the excised heart showed discrete cardiac uptake conforming to the in vivo image and gross pathologicl examination. (111)In platelet uptake in vegetations from the 17 animals averaged 240 ± 41 times greater than that in normal myocardium and 99 ± 15 times greater uptake in blood. In contrast, (111)In-leukocyte cardiac imaging showed no abnormal aortic valve uptake 24 hours after tracter administration and the lesion myocardium activity ratio was only 5 ± 2 (3 ± 1 for lesion/blood activity). Four normal rabbits demonstrated neither positive (111)In platelet scintigraphs nor abnormal cardiac tissue uptake. Likewise, noncellular (111)In was not concentrated to any significant extent in three animals with infective endocarditis. This study demonstrates that (111)In platelet, but not leukocyte cardiac imaging, is a sensitive technique for detecting experimental infective endocarditis. The imaging data conform to the cellular pathology of the infective endocarditis vegetation.