We used immunohistochemical techniques to demonstrate the distribution of receptors for the cytokine tumour necrosis factor-α on the popliteal lymph node and the adipose tissue surrounding it for 5 d following a simulated immune challenge to one hind leg in the rat. We found different patterns of expression of receptors on adipocytes surrounding a lymph node to a distance of about 1 mm, and on those more remote from the node. Sites recognised by an antibody to type I tumour necrosis factor receptors appeared on the challenged node and the adipocytes surrounding it within 30 min of an injection of bacterial lipopolysaccharide, but appeared on adipocytes surrounding the unchallenged popliteal node only 24 h later. Adipocytes distant from the node, both within the same depot and in the contralateral depot, showed no response. Sites recognised by an antibody to type II tumour necrosis factor receptors were present at all times on lymph nodes and the adipocytes close to them, but appeared on more distant adipocytes only 24 h after immune challenge, in both challenged and unchallenged legs. These data support the proposal, based on in vitro studies, that the adipose tissue surrounding major lymph nodes is specialised to respond to cytokines derived from lymphoid cells, and participates in the immune responses of the adjacent node.