The effects of diet on the composition and properties of adipose tissue in relation to lymph nodes were studied in adult guinea-pigs. The proportions of monoenoic triacylglycerol fatty acids were constant in all sites in adipose tissue of similarly fed guinea-pigs, but were substantially greater in samples from guinea-pigs fed on suet-enriched chow. Triacylglycerols in adipose tissue from near nodes contained significantly fewer saturated fatty acids, and significantly more 18:2n-6 and 18:3n-3 than those in samples from sites remote from nodes within the same depot. Depots that interact most strongly with lymphoid cells in vitro had the largest and most consistent within-depot differences. The gradients of triacylglycerol fatty acid composition with distance from lymph nodes in two small intermuscular depots were similar in guinea-pigs fed on plain or suet-enriched chow. These findings are consistent with the hypothesis that adipose tissue around lymph nodes is specialized for local interactions with the lymphoid cells therein, and help to explain the variability of serial or duplicate measurements of adipose tissue composition. When cultured alone, lipopolysaccharide-stimulated lymph node lymphoid cells from suet-fed guinea-pigs incorporated as much labelled thymidine as the controls. Adipose tissue explants from suet-fed guinea-pigs inhibited lymphocyte proliferation much less than those of the controls, although the site-specific differences were similar. The pattern of site-specific differences in glycerol released from explants incubated alone was generally similar for both dietary groups, but except in the popliteal depot, the increases following co-culturing with lymphoid cells were smaller for samples from suet-fed guinea-pigs. These experiments show that minor changes in the fatty acid composition of the diet can substantially alter the interactions between adipose tissue and lymphoid cells.