We have characterized the 24-h changes of insulin receptors on erythrocytes from patients with insulin-dependent diabetes of long duration. These diabetics were studied both in usual and poor metabolic control. Moreover, we have examined daytime changes of insulin receptors on monocytes from newly discovered diabetics. In both erythrocyte and monocyte studies, diabetics were compared to healthy controls. At insulin tracer concentration, insulin receptor binding to erythrocytes from diabetics in usual control and normal volunteers underwent a statistically significant diurnal variation with high binding values in the early morning, low daytime values with a nadir in the late afternoon, and a peak around midnight. Even diabetics in poor metabolic control due to insulin deprivation had preserved a similar 24-h rhythm of erythrocyte insulin receptors. Insulin receptor binding to monocytes at insulin tracer concentration declined significantly during the day both in newly discovered diabetics and in healthy controls. The mechanisms responsible for the acute phase changes of insulin-receptor binding are unknown, but the receptor changes seem related to the fed state. Moreover, analysis of the temporal interrelationship between erythrocyte insulin binding and plasma insulin concentration in diabetics during the 24-h period suggests that in these patients insulin may be one of the factors determining the rapid insulin receptor regulation.