Dietary fat has been incriminated as a positive risk factor for the development of neoplasia in human populations. We used adipose tissue fatty acid analysis as an index of dietary fat intake to study the association between dietary fat and immune function in a group of 94 free-living American males (avg age 47 years). Immunocompetence was tested by a battery of T- and B-lymphocyte stimulation tests and also by natural killer (NK) cell activity. Correlations were sought between fatty acid composition, plasma lipids, and immune responsivity. The degree of unsaturation of the diet over a polysaturated-to-saturated fat ratio range of 0.54-1.01 had no predictable effect on the immune function. Stepwise regression analysis showed that the concentrations of plasma triglycerides and cholesterol and its subfractions did not explain any of the variance in the immune tests. Palmitic acid (16:0) was associated with 7% of the variance of the response to C. albicans and E. coli, perhaps through influencing B-cell activity. Stearic acid (18:0) was correlated negatively to concanavalin A responsivity (18% of the variance) and positively to NK activity (20% of the variance). If impaired in vitro immune function is a marker of increased risk for carcinogenesis, then our data do not support a role for dietary fat influencing in any systematic manner lymphocyte function in vitro, as reflected by proliferative response or NK activity. Further, plasma lipoproteins, in particular cholesterol levels, did not appear to affect any immune function test. It remains to be studied whether dietary fat, lipoproteins, or fat-soluble substances may influence membrane structure and function and prostaglandin formation as alternative pathways in the promotion of neoplasia.