In our previous studies, we found that circulating thyroid hormone levels alter cholesterol partition between plasma and erythrocytes by changing the phospholipid content of erythrocytes (Ruggiero, F.M., et al. (1984) Horm. Metabol. Res. 16, 37-40; Ruggiero, F.M., et al. (1987) Lipids 22, 148-151). As an extension of this work, we now followed the exchange of free cholesterol between plasma and erythrocytes in control, hyperthyroid and hypothyroid rats under various experimental conditions in vitro. In control rats, erythrocytes incubated with plasma at 37°C for 4 hr lose 10% of cholesterol which was esterified by lecithin: cholesterol acyltransferase (LCAT) present in the plasma. In hyperthyroid rats, erythrocytes incubated with plasma lose 30% of cholesterol within the same time. By contrast, in the case of hypothyroid rats incubation for 4 hr was necessary to transfer 24% of free cholesterol from plasma to erythrocytes. Inhibition of cholesterol esterification did not affect the loss of erythrocyte cholesterol in control and in hyperthyroid rats. Ca increased the LCAT activity in the plasma of these rats. The findings shed light on the role of thyroid hormones in regulating cholesterol levels in plama through active cholesterol transfer between plasma and erythrocytes. [ABSTRACT FROM AUTHOR]