We evaluated the effect of the novel immunosuppressive agent, FK506, which is known to inhibit T cell immunity, on the development of lupus nephritis in MRL/MpJ-lpr/lpr (MRL/l) mice. FK506 was administered subcutaneously (1 mg/kg body weight) from 12 to 20 weeks of age in 13 MRL/l mice with spontaneous lupus nephritis. Nine animals receiving no treatment were used as the control. FK506 significantly reduced the development of proteinuria, lowered the level of BUN, and suppressed the elevation of serum anti-dsDNA antibodies. Histopathological study showed that FK506 significantly inhibited the progression of glomerular hypercellularity and crescent formation. Glomerular deposition of C3 was significantly reduced in the FK506-treated mice compared to the nontreated controls. These findings suggest that FK506 may protect against progression of lupus nephritis in MRL/l mice, an animal model of systemic lupus erythematosus.