Rates of whole body protein synthesis and catabolism in normal volunteers and in a group of severely septic patients were isotopically determined. In addition, the effect in the patients of either glucose infusion or total parenteral nutrition (TPN) on protein dynamics was assessed. The basal rate of net protein catabolism (NPC) was significantly higher in the septic patients than in the volunteers (p less than 0.05). The values obtained in the volunteers and patients were 1.44 +/- 0.18 and 2.20 +/- 0.10 g/kg/day, respectively. This increase in NPC was primarily due to a major increase in whole body catabolism that was partially counteracted by a modest increase in protein synthesis. When the patients were infused with glucose (4 mg/kg/min), NPC decreased significantly (p less than 0.001) to 1.96 +/- 0.08 g/kg/day, and during TPN the value was significantly lower again (p less than 0.04) (0.63 +/- 0.28 g/kg/day). In each instance the conservation of host tissue was due to an increase in protein synthesis: the accelerated rate of whole body protein catabolism continued irrespective of the nutritional status. The following conclusions were reached from these data: severely ill septic patients have an accelerated rate of NPC compared with normal volunteers, and this is primarily due to a large increase in whole body protein catabolism; TPN is an effective means of conserving host tissue in severely septic patients via the promotion of whole body protein synthesis; despite the beneficial effect of TPN in these patients, whole body protein catabolism continues unabated, and as a result, protein losses still occur at approximately one fourth the rate seen in the absence of TPN; and there is no obvious advantage in terms of protein-sparing when protein is provided in amounts exceeding 1.5 g/kg/day.