The effect of a lipid-rich diet was investigated in autoimmune NZB x W mice with immune complex lupus nephritis. Mice on an enriched lipid diet died sooner than controls. This increase in dietary fat elevated serum cholesterol levels and was associated with an accelerated loss of renal function. Ultrastructural examination of glomeruli revealed lipid in the peripheral loops and mesangium adjacent to immune deposits. Increased lipid accumulation was confirmed by histochemical staining and biochemical extraction. Accelerated disease was not related to changes in immune parameters. Thus, a high lipid consumption accelerated lupus nephritis by a local vascular effect and not by a systemic influence on the immune response. Therefore, in our system, a combined immunologic and lipid glomerular capillary insult caused a more rapidly progressive renal disease than immune complex injury alone.