1. The ability of diphtheria-tetanus-poliomyelitis-typhoid vaccination to induce modifications in protein metabolism was investigated in post-absorptive healthy humans. 2. Seven subjects were studied before and 2 days after vaccination. They underwent an intravenous primed constant infusion of L-[1-13C]leucine for 4h. Plasma protein concentrations, whole-body amino acid fluxes and acute-phase protein synthesis were determined. 3. Plasma concentrations of fibrinogen, alpha 1-acid glycoprotein, haptoglobin and alpha 1-antitrypsin were significantly elevated 2 days after vaccination (P < 0.05). Leucine oxidation was unaffected but whole-body protein synthesis and breakdown were both increased (P < 0.05), by 25 and 16% respectively, in subjects who had an elevated body temperature (n = 5). Albumin synthesis was unchanged, but hepatic synthesis of fibrinogen was 56% higher after vaccination. 4. The present investigation indicates that diphtheria-tetanus-poliomyelitis-typhoid vaccination could induce a sustained acute-phase reaction. Moreover, protein metabolism appeared to be extremely sensitive to a mild stress since leucine kinetics and fibrinogen synthesis were affected. Therefore, diphtheria-tetanus-poliomyelitis-typhoid vaccination might represent an attractive model for studying the inflammatory process in humans.