Intravenous glucose tolerance tests have demonstrated lower whole-body insulin sensitivity (S I) among African Americans (AA) compared with European Americans (EA). Whole-body S I represents both insulin-stimulated glucose disposal, primarily by skeletal muscle, and insulin's suppression of endogenous glucose production (EGP) by liver. A mathematical model was recently introduced that allows for distinction between disposal and hepatic S I. The purpose of this study was to examine specific indexes of S I among AA and EA women to determine whether lower whole-body S I in AA may be attributed to insulin action at muscle, liver, or both. Participants were 53 nondiabetic, premenopausal AA and EA women. Profiles of EGP and indexes of Disposal S I and Hepatic S I were calculated by mathematical modeling and incorporation of a stable isotope tracer ([6,6- 2H 2]glucose) into the intravenous glucose tolerance test. Body composition was assessed by dual-energy x-ray absorptiometry. After adjustment for percentage fat, both Disposal S I and Hepatic S I were lower among AA (P =.009 for both). Time profiles for serum insulin and EGP revealed higher peak insulin response and corresponding lower EGP among AA women compared with EA. Indexes from a recently introduced mathematical model suggest that lower whole-body S I among nondiabetic AA women is due to both hepatic and peripheral components. Despite lower Hepatic S I, AA displayed lower EGP, resulting from higher postchallenge insulin levels. Future research is needed to determine the physiological basis of lower insulin sensitivity among AA and its implications for type 2 diabetes mellitus risk. © 2012 Elsevier Inc.