We report the role of dietary glycine and the type of oil used as a vehicle in the hepatotoxicity of control rats and rats treated with 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153). In our first experiment, glycine or valine (as control) was fed in an unrefined diet at 5% for the entire study duration (5 days) to inhibit Kupffer cell activity. PCB-153 (100 or 300 μmol/kg) dissolved in medium chain triglyceride (MCT) oil, was injected intraperitoneally 2 days before euthanasia; the peroxisome proliferator Wy-14,643 was included as a positive control. MCT oil decreased cell proliferation by approximately 50%. PCB-153 slightly increased hepatic cell proliferation, but dietary glycine did not reduce cell proliferation. Because of the inhibition of cell proliferation in rats receiving MCT oil compared with rats receiving no injection, we hypothesized that MCT oil may have been inhibiting the hepatocyte proliferation in PCB-153-treated rats. We therefore performed another experiment using 3 types of oil as a vehicle for PCB-153: MCT oil, corn oil, and olive oil. Rats were injected with PCB-153 (300 μmol/kg) or one of the vehicles, again 2 days before euthanasia. MCT oil again decreased the hepatocyte proliferation by approximately 50%. In rats receiving PCB-153, hepatocyte proliferation was slightly higher than their respective vehicle controls for corn oil and olive oil but not for MCT oil. These studies show that the oil vehicle is important in cell proliferation after PCB exposure, with MCT oil appearing to be protective.