Experimental sepsis in rats induces a restriction in spontaneous food intake and a drop in liver glutathione, cytochrome P-450 (P-450) and aminopyrine demethylase (AD) activity. The present study was designed to assess the effects of antibiotics alone or when combined with food deprivation on these variables. Eighty-nine male Sprague-Dawley rats were assigned to six groups: control (C), acute infection (experimental pyelonephritis, I), acute infection with antibiotics and food given ad lib. (IA), control with antibiotics (CA), acute infection with antibiotics pair-fed to I (IAR), and sham-operated pair-fed to I (SR). Liver glutathione, P-450 and AD activities were reduced by 45·2, 79·8 and 41·2% respectively in group I. Glutathione and AD significantly increased only in those infected rats given antibiotics and allowed free access to food. P-450 did not normalize within the study period in infected rats receiving antibiotics and food repletion. The risk of drug hepatotoxicity in acute septic states is therefore closely related to the nutritional status. From this point of view, nutritional support is almost as important as treatment of infection.