Administration of oral vitamin A and the synthetic retinoids to humans and experimental animals has been accompanied by changes in lipid metabolism. These changes include alterations in serum, liver, and skin surface lipids. While the immediate cause(s) of the serum and liver changes remain(s) obscure, the skin surface lipid alterations appear to be secondary to changes in sebum production. The most marked effect of retinoid feeding seen in clinical or animal studies is that of hypertriglyceridemia. The increased serum triglycerides are found primarily in the very low-density lipoprotein (VLDL) fraction of the blood and occur during both the fasted and fed state. In rats, oral all-trans-retinoic acid, 13-cis-retinoic acid, and natural vitamin A have resulted in hypertriglyceridemia, while in man, 13-cis-retinoic acid, etretinate, and natural vitamin A have been reported to elicit this response. Current studies using the rat indicate that elevated serum triglycerides may be secondary to both increased liver secretion and decreased extrahepatic breakdown. Ongoing work from our laboratory and the possible primary causes of the systemic lipid changes are discussed.