Six healthy lean male adults, given a mixed meal containing 3190 kJ (16% from protein, 44% from carbohydrate and 40% from fat) were studied for the next 370 min using arteriovenous cannulation techniques across superficial and deep forearm tissues. The meal produced no significant change in forearm blood flow or skin temperature. The major differences between superficial and deep forearm tissues were (a) creatinine release by deep tissues but not superficial tissues; (b) the release of non-esterified fatty acids (NEFA) by superficial tissues and uptake by deep tissues; and (c) the more prolonged large positive arteriovenous concentration difference for glucose across deep than superficial tissues. The similarities were (a) general pattern of individual amino acid exchanges and transient positive amino acid N balance after meal ingestion; (b) consistent uptake of glutamate and release of glutamine (the main carrier of N out of superficial and deep forearm tissues); (c) the magnitude of the arteriovenous concentration differences for glucose, NEFA and total amino acids were related to the changes in their circulating concentrations and to the oxidation of carbohydrate, fat, and protein in the whole body; and (d) increases in the arterio–deep venous and arterio–superficial venous differences for glucose did not result in increased release of lactate, alanine or pyruvate, implying no increase in the activity of glucose–lactate and glucose–alanine cycles between forearm tissues and the liver. This study suggests that in a number of ways superficial and deep tissues can be regarded, at least qualitatively, as behaving as a ‘single metabolic unit’.