Visceral protein levels are used as indicators of prognosis, severity of injury, and nutritional status in hospitalized patients. Clinicians often use visceral protein levels to assess efficacy of nutritional support. The purpose of this study was to test the validity of such practices. Visceral protein levels were determined in patients in a medical ICU, head injury unit, and burn unit. The serum albumin and thyroxine-binding prealbumin (TBPA) levels correlated significantly with mortality in the medical ICU patients. Burn patients had depressed albumin and TBPA concentrations over the duration of hospitalization that related to the severity of thermal injury but not to adequacy of nutritional support. Head-injured patients had depressed admission albumin and TBPA levels, with neither protein level adequately related to caloric or protein supplementation. We conclude that visceral proteins may reflect severity of injury and prognosis in critically ill hospitalized patients, but they often do not accurately reflect nutritional status or adequacy of nutritional support.