OBJECTIVES: Our purpose was to test the hypothesis that bacterial endotoxin may reduce fetal growth and to assess some of the pathophysiologic mechanisms of such an effect. STUDY DESIGN: Two randomly selected groups of nine guinea pigs at 30 days' gestation were treated with a solution of endotoxin isolated from Bacteroides fragilis or with solvent alone. Antibody titers, glucose, triglycerides, and 6-keto-prostaglandin F1alpha were determined in maternal or fetal blood samples. Fetal weight was determined at 61 days' gestation. RESULTS: Endotoxin-treated guinea pigs showed positive antiendotoxin antibody titers, reduced weight gain, and significantly higher serum levels of triglycerides and 6-keto-prostaglandin F1alpha, but not of glucose, than did sham-treated controls. Fetuses of endotoxin-treated animals had significantly lower birth weights and serum glucose concentrations and significantly higher triglyceride levels than did control fetuses. CONCLUSIONS: Bacteroides fragilis endotoxin causes fetal growth retardation in the pregnant guinea pig, which may be due to alterations in carbohydrate and fat metabolism mediated by cytokine action.