Cyclosporine A (an immunosuppressive agent) decreases Ia lymphoid differentiation marker in female Sprague-Dawley rats with N-nitroso-N-methylurea-induced mammary tumors. Presence of lymphoid differentiation antigens was determined on mammary tumor cells and lymphoid cells from bone marrow, spleen, and peripheral blood by flow cytometric analysis. Quantification of Ia antigen expression was also performed by affinity chromatography and chromatofocusing in mammary tumors. A significant decrease in Ia antigen expression by mammary tumors of animals treated with cyclosporine A was noted with the two different methods. Cyclosporine A acts as an antagonist to prolactin receptors in such hormone-dependent mammary cancer. Our results should prove very useful in understanding the mechanisms of prolactin regulation of Ia antigen in tumorigenesis of the mammary gland.