Lipid-enriched diets have been related to a high cancer incidence in experimental animals for many years, and more recently, to assorted defects on the immune response. We investigated the effect of incubating human or murine (C3H/HEJ) lymphocytes with saturated (16:0) and unsaturated (18:1, 18:2, 18:3, 20:4) fatty acids (12 micrograms for each 10(7) cells), on the ability to cap with antihuman or antimouse anti-IgM, mu-chain specific antibody. Capping was also tested in obese (ob/ob, C57BL/6J) mice. Capping at 30 and 60 min was reduced by fatty acid incubation to 10-30% of control values in humans (p less than .001), and to 30% of control values in mice (p less than .01), regardless of degree of unsaturation. ob/ob capped normally. A lymphocyte membrane effect caused by fatty acids is observed in these experiments. Whether this is related to the dysimmunity caused by lipid diets cannot be assessed from our data, especially since all fatty acids, regardless of unsaturation, reduced the capping phenomenon.