Systemic lupus erythematosus is an immunologically mediated autoimmune disease which has been reported to be aggravated by certain environmental agents such as ultraviolet irradiation (UV). To further investigate this interaction, we examined the consequences of UV exposure on the autoimmune process of several strains of autoimmune mice. Strains of age- and sex-matched, 3- to 4-month old, autoimmune (MRL-lpr/lpr, (NZB x NZW)F1, BXSB) and nonautoimmune (BALB/c, B10.A) mice were shaved and exposed to an acute (2 h daily x 7 days) and a chronic (3 h/weekly x 4 weeks) dose of UV (FS40 lamps, 2 mJ/cm2/s). UV-induced changes in survival, autoantibody production, splenic B-cell activity, and target organ pathology were examined. After an acute UV exposure there were (10/15) deaths in the UV BXSB males and (4/15) in the UV BXSB females, compared to (1/15) in the non-UV BXSB male group and (0/15) in the non-UV BXSB females. No deaths occurred in the other UV autoimmune or nonautoimmune groups. Likewise, chronic UV resulted in increased UV BXSB male mortality (13/15) compared to UV BXSB females (2/15) and non-UV BXSB males and females. No deaths occurred in the other autoimmune (MRL-lpr/lpr, (NZB x NZW)F1) or nonautoimmune (BALB/c, B10.A) strains, after chronic UV exposure. Equivalent doses of Mylar-filtered FS40 UV (UVB deleted) resulted in no deaths in the UV BXSB male group. Acute and chronic UV also resulted in a significant increase in serum single-stranded DNA antibody production, splenic polyclonal B-cell activity, and renal glomerular inflammatory changes in the UV BXSB male mice. Thus, UV resulted in premature death and accelerated autoimmunity in UV BXSB males and may serve as a useful model for phototoxicity in autoimmunity.