In studies with bromobenzene we found increases in the activities of hepatic lysosomal enzymes. The present study was undertaken to determine how these changes are related to the development of hepatic injury after bromobenzene administration. A single intraperitoneal injection of bromobenzene (5 mmoles/kg) caused significant increases in the total activity of lysosomal N-acetyl-beta-glucosaminidase and beta-glucuronidase in rat liver within 8-12 h, whereas it did not alter the free activity of these enzymes. Enhancement of bromobenzene hepatotoxicity by the pretreatment of rats with phenobarbital was not associated with further changes in hepatic N-acetyl-beta-glucosaminidase or beta-glucuronidase activities. Cycloheximide administered prior to bromobenzene inhibited significantly the effect of bromobenzene on the total N-acetyl-beta-glucosaminidase activity. The results suggest that lysosomal enzymes are not directly involved in hepatic damage caused by bromobenzene and that the inhibition of protein synthesis may reduce this response to hepatotoxin.