In attempting to evaluate alterations in metabolic responses to dietary nutrients that occur in pathological conditions in man, it is first necessary to understand normal metabolic responses. The present study set out to determine the temporal responses of protein synthesis in the skeletal muscle of healthy subjects to the consumption of food. Sequential measurements of protein synthesis in quadriceps muscle were made in eight subjects by injection of 0.05 g L-[l-13C]leucine/kg body-weight. The rate of protein synthesis after an overnight fast (i.e. in the post-absorptive state) was 2.2% muscle protein. After 1 h of eating, protein synthesis was unaltered (2.2%/d), but after 10 h of consuming small hourly meals the rate had risen to 2.9%/d, with a variation in response among individuals. The response of muscle to 10 h of feeding was also investigated in subjects who underwent only one measurement each, either after 10 h of eating small meals or after the same time-period when no food was given. Protein synthesis rates were only slightly elevated in the group of fed individuals (2.3%/d, n 6) compared with the fasted group (2.1%/d, n 6). Taken together the two studies suggest that in healthy adults muscle protein synthesis does not respond quickly to the influx of dietary nutrients and that even after 10 h of feeding any stimulation of protein synthesis is small.