The mechanism by which TNF-α (tumour necrosis factor-α) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-α has been suggested to cause defects in capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-α concentrations, skin capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-α levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-α levels were associated with both capillary recruitment (r = -0.40, P = 0.02) and insulin sensitivity (r = -0.33, P = 0.05). In addition, capillary recruitment was associated with insulin sensitivity (r = 0.34, P = 0.04). Regression analysis showed that the association between TNF-α and insulin sensitivity [-0.527 mg · kg-1 of body weight · min-1 per pmol/l per pg/ml TNF-α (95% confidence interval, -1.066 to 0.011); P = 0.05] decreased by 30% after adjustment for capillary recruitment. In the children, neither capillary recruitment (r = 0.33, P = 0.2) nor insulin sensitivity (r = -0.24, P = 0.4) was significantly associated with TNF-α. In conclusion, in adults, but not in children, serum TNF-α levels are associated with capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-α and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.