We studied insulin binding to monocytes isolated from dieting and fasting young healthy persons during a 24-h period. In the persons who ate their usual food, we found a characteristic diurnal variation in the cellular insulin binding. Daytime insulin binding was low with a minimum in the afternoon; binding increased during the evening, reaching a maximum in the early morning. This variation seemed to be diet related, as total fasting abolished the circadian rhythm. Changes in cellular insulin binding were due to fluctuations in the binding affinity rather than alterations in receptor concentration. The circadian variation in insulin binding was grossly parallel to the well known variations in insulin sensitivity and glucose tolerance during the day.