The urinary excretion of 3-methylhistidine (3MEH) in humans and animals has been used as a biologic marker for skeletal muscle protein breakdown. In rats, it has been recently suggested that there is a significant contribution of 3MEH in urine from the gastrointestinal tract due to the rapid turnover of protein in that tissue. To evaluate this point in humans, six patients with short bowel were evaluated. They were placed on three-day meat-free diets while 24-hour urine collections were obtained. The mean +/- SEM 3MEH in the short-bowel group was 3.27 +/- 0.34 mumol/kg/d and the mean +/- SEM molar ratio of 3MEH to creatinine was 0.0212 +/- 0.0012. These data were not significantly different from the control group at 95% confidence level. The results suggest that the contribution of the small intestine appears to be negligible, therefore urinary 3MEH should continue to be a valid index of skeletal muscle breakdown in man.