The pathogenesis of the degenerative vascular disease and myocardial infarction that develop in mice with lupus-like disease was studied by immunofluorescence, light microscopy, and electron microscopy. Medium and small coronary arteries and arterioles of both infarcted and noninfarcted hearts had focal degenerative lesions consisting of deposits of periodic-acid--Schiff (PAS)-positive or eosinophilic material in the intima and to a lesser extent in the media, degenerative changes in the media without accompanying cellular inflammation, and occasional proliferation or swelling of intimal cells. These lesions often narrowed and, together with platelet aggregation, occasionally occluded the vascular lumens. Granular deposits of mouse immunoglobulin, C3, and occasionally gp70 were present in the walls of medium and small arteries, arterioles, and venules of both infarcted and noninfarcted myocardium. Dense deposits of foreign material were found by electron microscopy in areas corresponding to the immune deposits. These findings are consistent with the interpretation that these noninflammatory vascular lesions are caused by local deposition of antigen--antibody complexes. The immune-complex--mediated injury appears to lead to thrombotic and/or obliterative vascular changes that contribute to decrease of the coronary blood flow and to the development of myocardial infarction.