A model for the glucose-insulin control system has been developed. The primary controllers in this model are the pancreas and liver. These subsystems operate within the metabolic environment to maintain normal glucose levels. The prime control variables for each subsystem, as well as for systemic glucose utilization, are the plasma glucose and insulin concentrations perfusing these organs. A quantitative description of total system function can be obtained from systemic plasma glucose and insulin concentrations, but a clear understanding of individual subsystem function and interaction within the closed loop can only be obtained if each block is itself described quantitatively. The modeling approach focuses attention on those experimental procedures which will yield the input-output data necessary for this subsystem development in a dynamic sense. An experimental protocol has been developed which satisfies both the modeling requirements and physiological constraints involved in monitoring system variables for glucose control. Simultaneous input and output plasma concentrations have been obtained for the liver, pancreas, and periphery following glucose loading. Input-output dynamics for each block of the closed loop have been described in terms of the gain factors, time constants, and damping frequencies which are related to physiologic function. The feasibility of using such in vivo compartment analysis for the development of the overall glucose homeostatic mechanism has been demonstrated.