Effects of mild and severe hypervitaminosis A on retinol transport and clearance were studied in mature ewes. Excessive vitamin A intake was assoicated with high concentrations of vitamin A in plasma and liver, with elevated serum enzymes, with decreased feed consumption and packed cell volume, and with epithelial hyperplasia. Retinol transport in plasma increased 6- to 8-fold with excessive dietary vitamin A, was greater with mild hypervitaminosis A, and increased exponentially with vitamin A concentration in plasma. Clearance of retinol from plasma increased 2-fold with hypervitaminosis A, exhibited a greater response in the mild group, and increased linearly with vitamin A concentration in plasma. The relationship of clearance to vitamin A concentration in liver was described best by a power function. Retinol clearance represents a mechanism to maintain vitamin A concentration in plasma and may be most effective below vitamin A concentrations of 135 microgram/dl plasma. With severe hypervitaminosis A, massive vitamin A accumulates in liver leading to hepatic dysfunction and a resultant decrease in retinol clearance from plasma.