The effect of administration of 13-cis-retinoic acid (100 mg/kg diet) on lipid metabolism was examined in male rats fed either a 20% casein + 0.3% methionine diet, a 20% casein diet, a 10% casein + 0.3% methionine diet, or a 10% casein + 0.6% methionine diet for 10 days. Hepatic triglyceride concentrations of rats fed either 10% casein diet were 3-fold greater than animals receiving diets containing 20% casein. The addition of 13-cis-retinoic acid to the diet further increased the total hepatic lipid (43-56%) and triglyceride (approximately 2-fold) concentrations in rats fed the 10% casein diets. 13-cis-Retinoic acid supplementation did not alter the total liver lipid or triglyceride concentrations in rats fed either of the 20% casein diets. Thus, under specific dietary conditions, the administration of 13-cis-retinoic acid resulted in a marked accumulation of hepatic lipids which did not appear to be related to the total methionine content of the diet nor to the hepatic concentrations of S-adenosylmethionine and glutathione. In addition, all four groups of 13-cis-retinoic acid-fed rats exhibited elevations in the concentration of serum triglycerides, and 10-20% reductions in serum cholesterol concentrations.