Spontaneous lipolysis in the adipocytes surrounding the popliteal lymph node rose within 1 h of its being activated with a subcutaneous injection of lipopolysaccharide (LPS), reached a peak after 6-9 h, then declined almost to basal levels after 24 h. The response of adipocytes from elsewhere in the same depot was delayed and smaller. Following the simulated immune challenge, perinodal adipocytes were consistently more sensitive to noradrenalin at 10(-8) and 10(-7) M than those elsewhere in the same depot, but the maximum lipolysis, in the presence of 10(-5) M noradrenalin, was similar in all popliteal samples. These effects were increased by incubating adipose tissue explants for 24 h in tissue culture medium, suggesting autocrine amplification of the initial stimuli. Incubation with interleukin-4 (IL-4, 10 ng/ml) abolished the increase in lipolysis in samples around the activated lymph node and depressed it to below control values in other adipocytes. In vivo stimulation of the popliteal node increased maximum lipolysis in the presence of 10(-5) M noradrenalin in samples from around mesenteric lymph nodes and after 24 h incubation, in omental perinodal adipocytes. No effects of any pre-treatments were detected in perirenal adipocytes. We conclude that the adipocytes surrounding lymph nodes are actively involved in local, transient immune responses. Their participation may explain why most major lymph nodes are embedded in adipose tissue.