The effects of feeding beef suet (mostly saturated and monoenoic fatty acids), sunflower oil (rich in n-6 fatty acids) and fish oil (rich in n-3 fatty acids) on the response of mesenteric, omental, popliteal and perirenal adipocytes to experimentally-induced local inflammation were studied in adult guinea pigs. After 6 weeks on the experimental diets, the animals were fed standard chow, and lipopolysaccharide was injected unilaterally daily for 4 d to induce swelling of one popliteal lymph node. Basal lipolysis in the perinodal adipocytes of all depots studied was higher in the sunflower oil-fed animals than in the controls fed on standard chow, and lower in those fed on suet or fish oil. Dietary lipids altered rates of lipolysis during incubation with 10-5 M noradrenaline in all samples studied from the locally-activated popliteal depot, but only in adipocytes within 5 mm of a large lymph node in the other depots. The fish-oil diet attenuated the spread of increased lipolysis within the locally-activated popliteal adipose tissue, and from this depot to other node-containing depots. These experiments show that n-6 polyunsaturated fatty acids promote and n-3 fatty acids suppress the spread of immune activation to adipocytes within and between depots, and alter the sensitivity of perinodal adipocytes to noradrenaline. Dietary effects are reduced or absent in adipocytes in sites remote from lymph nodes, and thus such samples do not adequately represent processes in perinodal adipose tissue. These results are consistent with the hypothesis that perinodal adipocytes interact with adjacent lymphoid cells during immune responses.