In the present study, rats were fasted for 3 days and subsequently refed for 1, 3, or 5 days. Measurements of insulin binding to its receptors on liver plasma membranes were carried out in conjunction with measurements of the activity of an insulin-regulated enzyme from liver cytosol, glucokinase. In response to the 3-day fast (chronic hypoinsulinemia), the insulin receptor number almost tripled, whereas the glucokinase activity was halved. The insulin receptor number slowly fell to control values during the 5 days of refeeding. In contrast, glucokinase activity rose to levels 2.5 times higher than control (5 times higher than the fasting values) after 1 day of refeeding. Altough the activity fell off somewhat during refeeding it was still dobule control values after 5 days refeeding. It was concluded that in the fasted rat there was a dissociation between insulin receptor concentration and the activity of the insulin-regulated enzyme glucokinase. However, the fasting-induced increase in receptor concentration appeared to play a permissive role in the rapid overshoot of glucokinase activity observed in the early stages of refeeding. Such a scheme would explain the metabolic changes occurring in the fasted-refed rat.