In this report a new approach is introduced that allows estimation of insulin sensitivity (S(I)) from orally ingested glucose during an oral glucose tolerance test (OGTT) or a meal glucose tolerance test (MGTT) in normal subjects. The method hinges on the classic minimal model of glucose kinetics that is coupled with an equation describing the rate of appearance of glucose into the circulation after oral glucose ingestion. The model provides an estimate of S(I) in a given individual based on simple area under the curve type of calculations. To prove the reliability of the new approach, MGTT studies performed in 10 normal subjects were analyzed and the S(I) index from the MGTT was compared with the S(I) index obtained in the same subjects from an insulin-modified, frequently sampled iv glucose test (FSIGT). S(I) from the MGTT was 13.6+/-3.9 x 10(-4) dL/kg x min/microU x mL and was strongly correlated to the S(I) from the FSIGT (rs = 0.89; P < 0.01). In conclusion, this study shows that in normal subjects the minimal model can be applied to a MGTT/OGTT to derive an index of insulin sensitivity that is in good agreement with the one estimated from the FSIGT. Due to its simplicity, this method has potential for use in population studies, but further investigation is required to ascertain its applicability to subjects with severe insulin resistance and impaired secretory function.