Young adult Wistar rats received 40 mg/kg of cyclosporin perorally for 21 days. Cyclosporin induced almost total disappearance of thymic medulla, whereas the cortex remained preserved. Although the density of cortical macrophages did not change significantly, their characteristics altered markedly and they became enlarged and rounded. In addition to an increase in acid phosphatase and nonspecific esterase activities, cortical macrophages developed very strong succinic dehydrogenase and chloroacetate esterase activities and a fine, granular, aldehyde fuchsin-positive cytoplasmic content. However, these cytoplasmic granules were PAS-negative and were not sudanophilic. Cortical macrophages retained their normal antigenic properties (which were studied by the use of ED1, ED2 and R-MC 41 monoclonal antibodies). Phagocytic cells in the remaining medullary islands retained their usual characteristics. The changes in cortical macrophages after cyclosporin treatment are discussed, especially in relation to the characteristics of macrophages of the cortico-medullary zone in the normal rat thymus.