To determine the effect of an anaesthetic with antioxidant potential, propofol, on red blood cell (RBC) antioxidant enzyme activities and RBC susceptibility to peroxidative challenge. Propofol was administered by intravenous bolus (2.5 mg.kg-1) and continuous infusion (36 and 72 ml.hr-1 in nine swine; 216 ml.hr-1 in two swine), to achieve serum concentrations between 5 and 30 micrograms.ml-1 for two hours at each rate. Arterial blood sampling was at 0, 10, 30, 60, and 120 min for each rate of infusion, for measurement of plasma propofol concentration, activities of plasma and RBC superoxide dismutase, glutathione peroxidase, glutathione reductase, RBC catalase, and RBC malondialdehyde (MDA) formation in response to ex vivo oxidative challenge with t-butyl hydrogen peroxide (tBHP; 1.5 mM). Antioxidant mechanisms were determined by in vitro study of MDA formation, GSH depletion, and oxidation of haemoglobin to methaemoglobin in human erythrocytes exposed to propofol 0-75 microM. The antioxidant potential of propofol was compared with that of alpha-tocopherol utilising the reaction with 2,4,6-tripyridyl-s-triazine (TPTZ). Propofol had no effect on plasma or RBC antioxidant enzyme activities. It inhibited RBC MDA production over the range of 0-20 micrograms.ml-1 (y = -18.683x + 85.431; R2 = 0.8174). Effective propofol concentrations for 25% and 50% reductions in MDA levels were 7-12 and 12-20 micrograms.ml-1, respectively. Propofol has a similar effect on human erythrocytes in vitro (R2 = 0.98). Propofol antagonises the effects of forced peroxidation of red cells at anaesthetic and sub-anaesthetic concentrations in swine. Its actions include scavenging of oxygen derived free radicals in a tocopherol-like manner.