To investigate the influence of different dietary fats on lipids and anti-cardiolipin antibody levels, autoimmune NZB/W F1 mice were fed on diets containing 200 g dietary fat as palm oil, lard–soyabean oil (1:1, w/w), soyabean oil, rapeseed oil or fish oil/kg. In addition, each dietary fat group was divided into an early-feeding group with feeding from 2 months of age, and a late-feeding group with feeding from 5 months of age. Serum levels of triacylglycerol, phospholipid, cholesterol and anti-cardiolipin antibody were measured at regular intervals, and mice were killed at the age of 7 months for analysis of hepatic lipid and fatty acids. The results showed that hepatic triacylglycerol and cholesterol contents were lower in mice fed on fish oil than in those fed on palm oil. In contrast, hepatic phospholipid content was higher in mice of the fish oil group than in those of the other four dietary fat groups. Composition profiles for both hepatic and renal oleic acid (18:1n-9), linoleic acid (18:2n-6) and eicosapentaenoic acid (20:5n-3) were similar to those of the dietary fats in mice of both early-feeding and late-feeding groups. Fish oil intake decreased arachidonic acid (20:4n-6) concentration in kidney tissue but not in liver tissue. Serum triacylglycerol, cholesterol and phospholipid levels were lower in mice fed on fish oil than in those fed on palm oil. Immunoglobulin (Ig) M anti-cardiolipin antibody was lower for the fish oil group than for the other groups. The IgG anti-cardiolipin antibody level was significantly lower in mice fed on fish oil compared with that of the palm oil group only in the early-feeding group. There was a positive correlation between serum IgM anti-cardiolipin antibody and phospholipid levels (early-feeding group r 0·902, P < 0·05; late-feeding group r 0·894, P < 0·05). These findings suggest dietary fish oil may affect both lipid levels and anti-cardiolipin antibody, contributing to alleviation of the autoimmune process in autoimmune-prone NZB×NZW F1 mice.