OBJECTIVE: To explore the underlying physiology of hostility (HOST) and to test the hypothesis that HOST has a greater impact on fasting glucose in African American (AA) women than it does on AA men or white men or women, using an intravenous glucose tolerance test (IVGTT) and the minimal model of glucose kinetics. METHODS: A total of 115 healthy subjects selected for high or low scores on the 27 item Cook Medley HOST Scale underwent an IVGTT. Fasting nonesterified fatty acids (NEFA) levels were measured before the IVGTT. Catecholamine levels were measured 10 minutes into the IVGTT. RESULTS: Moderation by group (AA women versus others) of HOST was found for glucose effectiveness (Sg, p = .02), acute insulin response (AIRg, p = .02), and disposition index (DI, p = .02). AA women showed a negative association between HOST and both Sg (beta = -0.45, p = .04) and DI (beta = -0.49, p = .02), controlling for age and body mass index. HOST was also associated with changes in epinephrine (beta = 0.39, p = .05) and fasting NEFA (beta = 0.44, p = .02) in the AA women. Controlling for fasting NEFA reduced the effect of HOST on both Sg and DI. CONCLUSIONS: This study shows that HOST is related to decreased DI, a measure of pancreatic compensation for increased insulin resistance as well as decreased Sg, a measure of noninsulin-mediated glucose transport compared in AA women. These effects are partly mediated by the relationship of HOST to fasting NEFA.