Changes in whole-body protein metabolism due to several skeletal trauma were estimated in five male volunteers and four male trauma patients using a single pulse of [15N]alanine and [13C]urea. The isotopic decay data were computer curve-fitted to obtain the best estimates for eight parameters of a four-pool model. The trauma patients excreted almost 5 times as much urinary nitrogen and utilized 33% more energy than did the volunteers on the same hypocaloric, protein-free diet. Trauma was found to expand the "active metabolic nitrogen" pool and the transfer rates of nitrogen into and out of a "slow turnover protein" pool. Whole-body protein synthesis increased 37% above normal and protein breakdown increased 79% above normal due to trauma. These values were in agreement with those determined at the same time using a [14C]leucine continuous infusion method. The data show that trauma accelerates the nitrogen flow and both protein synthesis and breakdown. This mechanism for negative nitrogen balance is consistent with that found for other severe stresses but is different from milder stresses.