Effects on the liver and liver lipids were evaluated in groups of male and female Fischer 344 rats (5/sex/dose level) fed nominal levels of 0, 0.6, 1.2 or 2.5% di-n-butyl phthalate in the diet for 21 days. Toxicity was evident by statistical differences between dosed groups and controls for: mean body weights (2.5% and 1.2% group males & 2.5% group females), food consumption (2.5% group males & females), absolute and relative liver weights (all treated animals), relative kidney weights (1.2 and 2.5% group males & 2.5% group females) and absolute and relative testis weights (2.5% group males). There was a statistically significant decrease in serum cholesterol (all treated animals) and a significant decrease in serum triglycerides (all treated males), although these effects were not considered dose-related. Also observed was an significant increase in serum triglycerides for 2.5% group females. There was a moderate increase in peroxisome proliferation for the high dose animals. Liver biochemistry revealed statistically significant differences between treated and controls as indicated by cyanide-insensitive palmitoyl-CoA oxidation levels (1.2 and 2.5% group males & 2.5% group females), lauric acid 11- and 12- hydroxylase activities (all treated males & 2.5% group females) and total hepatic protein levels (0.6 and 1.2% group males, 1.2 and 2.5% group females). There was no consistent dose response relationship among treatment groups for lipid content in the liver. Histological changes attributable to di-n-butyl phthalate were reduction in cytoplasmic basophilia in the livers of the high dose rats and some of the 1.2% group males. Severe testicular atrophy was observed at the 2.5% dietary level.