The pharmacological effects of prolonged administration of a corticosteroid, betamethasone, and active vitamin D3 [1,24R-(OH)2D3] on lymphoproliferation and autoimmune disease of MRL/MP-lpr/lpr (MRL/1) mice were examined. Relatively high doses of betamethasone (0.25 mg/kg/day) prevented lymphoproliferation, reduced serum levels of anti-dsDNA, anti-ssDNA, and anti-poly (ADP-ribose) antibodies, and brought about clinical improvement, such as reduced proteinuria and diminution of skin lesions. It is noteworthy that not only did prevention of lymphoproliferation occur, but also recovery of the Lyt-2+ T cell subset in the thymus and the spleen was observed. The administration of 1,24R-(OH)2D3 (0.1 microgram/kg/day) similarly prevented proteinuria, and produced recovery of a Lyt-2+ subset in the thymus.