The effect of high- and low-fat diets with different levels of fatty acid unsaturation on insulin receptors of erythrocyte ghosts was studied during different phases of the menstrual cycle in 31 healthy premenopausal women. Subjects were divided into two groups and consumed controlled diets containing 39% fat with a ratio of polyunsaturated to saturated fatty acids (P:S) of either 0.30 or 1.00 for four menstrual cycles. They were switched to 19% fat at the same P:S for another four cycles. Fasting blood samples were collected during the follicular and luteal phases. Insulin receptors were measured from right-side-out ghosts. Insulin binding was significantly lower due to fewer receptors when subjects were fed the low-fat, high-carbohydrate diet compared with the high-fat, low-carbohydrate diet. There was no significant effect of level of unsaturation or time of menstrual cycle on insulin binding. Thus, insulin receptors on erythrocytes respond to dietary lipids.