As revealed with ED1 and ED2 monoclonal antibodies, macrophages are scattered throughout the thymic tissue. However, in contrast to the cortex and medulla, in the cortico-medullary zone macrophages are large and show strong reactivity with rabbit polyclonal antisera to cyclooxygenase. Only few smaller cortical macrophages also show weaker presence of prostaglandin synthase. After cyclosporin treatment cortical macrophages become strikingly similar to the macrophages of the cortico-medullary zone of the normal thymus. Cortical macrophages become enlarged and develop the strong expression of prostaglandin synthase. Our results show that a specific type of macrophages (with distinct histochemical characteristics, enzyme profile and ultrastructural organization, which is strategically positioned within the thymic tissue--as we demonstrated earlier) possesses the enzyme capacity required for prostaglandin synthesis. After cyclosporin treatment, which interferes with the maturation of thymocytes, cortical macrophages thoroughly change and develop the strong prostaglandin synthase expression, similar to that of normal cortico-medullary zone macrophages.