The JCR:LA-corpulent male rat, when homozygous for the cp gene (cp/cp) is hyperlipidemic and prone to atherosclerosis. Both male and female cp/cp rats have markedly elevated serum levels of triacylglycerols and phospholipids [Dolphin, P.J. et al. 1987. Biochim. Biophys. Acta. 919: 140-148]. In the present study, monolayer cultures of hepatocytes were prepared from male and female, corpulent and lean, rats. There was a marked hypersecretion of all very low density lipoprotein (VLDL) lipid and apoprotein components from corpulent-derived cells. The increased secretion most likely accounts for the increased levels of VLDL lipids and apoproteins previously observed in serum. In contrast, there was no difference between the corpulent and lean hepatocytes in their secretion of high density lipoprotein (HDL) lipids and apoproteins. The difference in triacylglycerol secretion between the lean and corpulent cells was sustained even when the cells were cultured for 24, 48, and 72 h prior to the experiment, by which time the hormonal differences between the corpulent and lean animals would have been largely eliminated. The magnitude of the difference in triacyglycerol secretion did not diminish with increasing time in culture. The biochemical basis responsible for the hypersecretion of VLDL has not yet been established. However, preliminary results suggest that there is an inherent difference in glycerolipid metabolism in the two types of hepatocytes.