Vitamin A and other retinoids are known to have an effect on biological membranes. We measured the effects of retinol, retinoic acid and retinyl palmitate on in vitro osmotic fragility, spontaneous hemolysis and membrane microviscosity of human red blood cells (RBC)., Incorporation of retinol into the erythrocyte membrane was also studied. The effect of large doses of retinol on adenosine dinucleatide phosphate (ADP) and collagen-induced platelet aggregation was also measured. The results demonstrate that all three retinoids induce alterations in RBC manifested by increased osmotic fragility, spontaneous hemolysis and membrane microviscosity. Retinol incorporation into the RBC membrane was dose-dependent and saturable. The second phase of ADP induced platelet aggregation was markedly depressed by retinol while having no effect on collagen induced platelet aggregation. Retinoid administration to rats induced similar in vivo RBC alterations as was seen with retinoid treatment in vitro.