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A two-compartment minimal model (2CMM) has been proposed [A. Caumo and C. Cobelli.Am. J. Physiol. 264 (Endocrinol. Metab. 27): E829–E841, 1993] to describe intravenous glucose tolerance test (IVGTT) labeled (hereafter hot) glucose kinetics. This model, at variance with the one-compartment minimal model (1CMM), allows the estimation of a plausible profile of glucose production. The aim of this study is to show that the 2CMM also allows the assessment of insulin sensitivity (), glucose effectiveness (), and plasma clearance rate (PCR). The 2CMM was identified on stable-isotope IVGTTs performed in normal subjects (n = 14). Results were (means ± SE) = 0.85 ± 0.14 ml ⋅ kg⁻¹ ⋅ min⁻¹, PCR = 2.02 ± 0.14 ml ⋅ kg⁻¹ ⋅ min⁻¹, and = 13.83 ± 2.54 × 10⁻²ml ⋅ kg⁻¹ ⋅ min⁻¹ ⋅ μU⁻¹ ⋅ ml. The 1CMM was also identified; glucose effectiveness and insulin sensitivity indexes were V = 1.36 ± 0.08 ml ⋅ kg⁻¹ ⋅ min⁻¹and …