Recent reports have indicated that guinea pig may be a better model for the study of benzoate conjugation in humans because of the presence of a salicylate-activating ligase. We gave intraperitoneal injections of sodium benzoate, sodium salicylate, sodium methylprednisolone and sodium phenobarbital for 4 consecutive days to groups of weanling guinea pigs before sacrifice. A measurement of benzoyl-CoA ligase activity and in vitro hippurate synthesis was done in liver and kidney cortex homogenates from each treated group at 21 days of age, as compared to an untreated (saline) 21-day control group. The results indicate that benzoyl-CoA ligase in guinea pigs is affected by phenobarbital (liver and kidney; p < 0.05-0.01) and methylprednisolone (liver; p < 0.01). Liver hippurate synthesis was also significantly induced by phenobarbital (p < 0.01). Both these treated groups also had reduced levels of free carnitine in plasma taken from 21-day-old guinea pigs as compared to the untreated control. Sodium benzoate did not have any effect on benzoyl-CoA ligase activity or on in vitro hippurate synthesis. However, sodium salicylate did show some effect on the induction of liver and kidney benzoyl-CoA ligase (not significant) and liver (p < 0.05) and kidney hippurate synthesis. It is important that studies on the guinea pig model be extended for application to children receiving therapy of benzoate and other aromatic acids like p-aminobenzoate or salicylate.