The physiological bases for roles of adipose tissue and fatty acids in the symptoms and dietary treatments of Crohn's disease are poorly understood. The hypothesis developed from experiments on rodents that perinodal adipocytes are specialized to provision adjacent lymphoid tissues was tested by comparing the composition of triacylglycerol fatty acids in homologous samples of mesenteric adipose tissue and lymph nodes from patients with or without Crohn's disease. Mesenteric perinodal and other adipose tissue, and lymph nodes, were collected during elective surgery for Crohn's disease and other conditions. Fatty acids were extracted, identified, and quantified by thin-layer and gas-liquid chromatography. Perinodal adipose tissue contained more unsaturated fatty acids than other adipose tissue in controls, as reported for other mammals, but site-specific differences were absent in Crohn's disease. Lipids from adipose and lymphoid tissues had more saturated fatty acids, but fewer polyunsaturates in Crohn's disease patients than controls. In adipose tissue samples, depletion of n-3 polyunsaturates was greatest, but n-6 polyunsaturates, particularly arachidonic acid, were preferentially reduced in lymphoid cells. Ratios of n-6/n-3 polyunsaturates were higher in adipose tissue but lower in lymphoid cells in Crohn's disease patients than in controls. Site-specific differences in fatty acid composition in normal human mesentery are consistent with local interactions between lymph node lymphoid cells and adjacent adipose tissue. But these site-specific properties are absent in Crohn's disease, causing anomalies in composition of lymphoid cell fatty acids, which may explain the efficacy of elemental diets containing oils rich in n-6 polyunsaturates.