Female B/W mice spontaneously develop an autoimmune disease that is similar to systemic lupus erythematosus. Antibodies to doublestranded DNA (dsDNA) and antinuclear antibodies develop in aging animals; death from immune complex-mediated glomerulonephritis occurs from 8 to 12 mo of age. It has been reported that prostaglandin (PG)E(1) treatment of such mice prolongs survival. In the present study, four groups of female B/W mice were studied beginning at 6-11 wk of age on the following regimens: (a) a synthetic diet that contained 20% safflower oil, (b) a standard laboratory chow diet, (c) a standard diet together with injections of PGE(1), and (d) an essential fatty acid-deficient synthetic diet that contained 20% coconut oil. All animals were tested monthly for antinuclear antibodies and anti-dsDNA. Kidney tissue was obtained for light and immunofluorescence microscopy when animals were dying. All disease manifestations were altered strikingly in the essential fatty acid (EFA)-deficient animals. Intermediate benefit was seen in PGE(1)-treated animals. 7% of the control animals and 18% of safflower oil-fed animals survived to 10 mo. In contrast, the PGE(1)-treated and EFA-deficient mice had a similar survival rate (78-88%). At age 16 mo, 78% of EFA-deficient mice and 45% of PGE(1)-treated mice were alive. 25% of the PGE(1)-treated and 55% of the EFA-deficient animals survived to 20 mo. Serum anti-dsDNA appeared at age 5 mo in safflower oil-fed and control animals, but not until 9 and 12 mo for PGE(1)-treated and EFA-deficient animals, respectively. All kidneys from 7- to 9-mo-old safflower oil-fed and control animals and the majority of kidneys from PGE(1)-treated animals were abnormal by light and immunofluorescence microscopy. Kidneys from EFA-deficient animals were essentially normal at 10 mo. At 13 mo, all PGE(1)-treated animals examined had significant kidney involvement, whereas none of the EFA-deficient animals had glomerulonephritis. These findings demonstrate that an EFA-deficient diet has a beneficial effect on murine lupus erythematosus.