As a basis for studies of the influence of lipids on the immune response and health, adult C57 BI mice were fed for 10 weeks or longer on one of the following diets: high (200 g/kg) polyunsaturated fatty acid, high (200 g/kg) saturated fatty acid and low (50 g/kg) polyunsaturated fatty acid purified diets and a standard commercial diet. The three test-fat diets were compounded to have approximately the same energy content and the mice of each group maintained similar body-weights. High-fat diets significantly reduced their subsequent delayed hypersensitivity response to challenge after sensitization with tuberculin. Immunoglobulin (Ig)M antibody formation against Escherichia coli lipopolysaccaride was transiently decreased, but IgG antibody against sheep erythrocytes and killed salmonella vaccine, IgG and IgE antibodies against ovalbumin remained unaffected. Total and differential blood counts revealed no differences between mice on high-fat and control diets in either the absolute numbers or the proportions of the types of leukocytes. Studies on peritoneal macrophages from mice of each group showed no difference in morphology and they ingested non-toxic and toxic particles releasing similar amounts of lactate dehydrogenase (EC 1.1.1.27) and β-glucuronidase (EC 3.2.1.31) for each substance, indicating that there were no differences in viability or phagocytic function. The present study shows that the C57 BI mouse can provide a model for the investigation of some consequence of the reduced immunocompetence induced by high-fat diets.