The murine strain MRL/1 spontaneously develops a systemic lupus erythematosus (SLE)-like syndrome. An increased number of T cells and polyclonal T helper cell activity has been described in these mice suggesting a potential role for 1,25-dihydroxyvitamin-D3[1,25-D3], an antiproliferative hormone selecting the T-helper lymphocyte subset. One month old MRL/1 mice were submitted or not to 1,25-D30.1μg for 4 weeks, then 0.15μg given i.p. every other day for 18 weeks while maintained on a low calcium chow. Dermatologic lesions, i.e. alopecia, necrosis of the ear and scab formation, were completely inhibited by 1,25-D3therapy. By 20 weeks, all mice had developed proteinuria. However, the degree of proteinuria was somewhat reduced in treated mice as assessed by urine protein/creatinine ratios (4 in treated vs untreated mice respectively). Moreover, a trend for a reduction in serum titers for anti-ssDNA antibodies was observed at 18 weeks. The active vitamin D metabolite had no effect on the development of the generalized lymphoid hyperplasia. Hypercalcemia developed when 1,25-D3was increased to 0.15/μg (2.62±0.12 vs 1.97±0.07 mmol/1, treated vs untreated mice respectively). These results suggest a beneficial role of 1,25-D3in the prevention or attenutation of some manifestations of murine SLE, a model sharing many immunologic features with human SLE.