1. Thirty-three arteriovenous forearm catheterization studies were carried out in 19 lean subjects starving for 12-14 h (n = 13), 30-36 h (n = 7) and 60-66 h (n = 13). Forearm blood flow was measured in order to calculate the flux of various substrates. At the same time, whole-body oxidation of fat, carbohydrate and protein was calculated using indirect calorimetry and urinary nitrogen excretion. 2. After an overnight fast (12-14 h), whole-body resting energy expenditure was accounted for by the oxidation of protein (15%), carbohydrate (17%) and fat (68%). At 30-36 h and 60-66 h of starvation, essentially all the non-protein energy was derived from the oxidation of fat (directly plus indirectly via ketone bodies). 3. After an overnight fast, acetoacetate and 3-hydroxybutyrate were taken up by forearm muscle at a rate which could account for 5% of the resting O2 consumption of this tissue. As starvation progressed, forearm muscle took up more acetoacetate and released 3-hydroxybutyrate so that the net uptake of ketone bodies was sufficient to account for about 10% of the resting O2 consumption at 30-36 h of starvation and about 20% at 60-66 h of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)