Individual and combined effects of dietary protein and butylated hydroxytoluene (BHT) were investigated. Groups of young, female rats were fed diets containing 24, 8, or 4% protein for 5 weeks. During the fifth week, BHT was administered intragastrically to half the rats in each group at 250 mg/kg/day for 7 days. Reduction of protein intake, particularly to 4% dietary level, caused significant reduction in body weight gain, relative liver weight, hepatic microsomal cytochrome P-450, liver total protein, and serum albumin concentration as well as elevation of hepatic glucose-6-phosphatase activity, relative heart weight, and serum globulin concentration. BHT treatment, on the other hand, caused significant reduction in body weight gain and glucose-6-phosphatase activity as well as liver enlargement, induction of hepatic microsomal protein and cytochrome P-450, and elevation of serum total cholesterol level. Several effects of BHT intensified as protein intake was reduced. In addition, reduction of relative spleen weight and liver necrosis were observed only among the BHT-treated rats fed 4% dietary protein. It was concluded that combination of protein deprivation and BHT treatment produced responses that are significantly greater than the sum of the corresponding responses produced by the individual treatments.