Rat aortic allografts immunosuppressed with cyclosporin--but not with azathioprine or steroids--develop an early inflammatory lesion in the subendothelial space. This "endothelialitis" is followed by an influx of proliferating smooth muscle cells into the intima, resulting in intimal thickening and accelerated arteriosclerosis. Administration of azathioprine and steroids largely ameliorates the development of the accelerated lesion. Similar endothelialitis and accelerated arteriosclerosis have been observed previously in the autopsy material of cardiac transplant recipients. Our results confirm the suggestion that the development of accelerated allograft arteriosclerosis is most likely linked to cyclosporin administration.