Hepatocyte cytoplasmic alterations were stereologically determined in male and female Sprague-Dawley rats fed PCB congener 128 (2,2',3,3',4,4'-hexachlorobiphenyl) in concentrations of 0.05, 0.5, 5, 50 ppm, or corn oil in diets daily for 13 weeks. A significant increase (p < 0.05) in the volume-fraction of smooth endoplasmic reticulum (SER) was measured in the female rats fed a diet containing 5 or 50 ppm of the congener and a significant increase was revealed in the male rats at doses of 0.5 and 50 ppm. Because drug metabolizing enzymes are bound to the SER, proliferated profiles may imply heightened enzyme activity necessary to metabolize the PCB. An elevation in volume-fraction of rough endoplasmic reticulum (RER) was measured in the hepatocytes of the male rats fed 5 ppm of the congener and none of the concentrations significantly enhanced the level of RER profiles in the females. The volume-fraction values of mitochondria, peroxisomes or lipid droplets of the hepatocytes in either the males or the females were not significantly different, as were the baseline volume-fraction of parameters studied between the male and the female rats. We determined for PCB 128, when administered in a diet to Sprague-Dawley rats, the no observable adverse effect level (NOAEL) is < 0.5 ppm.