OBJECTIVE - The purpose of the present Study was to validate Various surrogate estimates of insulin sensitivity (IS) in a renal transplant Population and to assess the influence of immunosuppressive and antihypertensive therapy on insulin resistance (IR) after renal transplantation. RESEARCH DESIGN AND METHODS - A total of 167 consecutive renal transplant recipients without previously known diabetes underwent a 75-g oral glucose tolerance test (OGTT) 3 months after renal transplantation. A total of 43 Patients also underwent a euglycemic-hyperinsulinernic glucose clamp study. Six OGTT-derived IS indexes were validated against the euglycemic-hyperinsulinernic glucose clamp-derived IS index (ISICLAMP). RESULTS - The OGTT-derived ISITX correlated closely with the ISICLAMP (r = 0.58, P < 0.001). The other surrogate estimates of IS were also significantly but less well correlated With the ISICLAMP (Spearman's correlation r = -0.45 to 0.41, P = 0.003-0.050). In the univariate model, BMI, daily prednisolone dose, creatinine clearance, hypertension, number of antihypertensive agents, and use of diuretics or <beta>-blockers were negatively associated with ISITX (P < 0.05). After multiple regression analysis, BMI (P < 0.001), daily prednisolone dose (P < 0.001), cytomegalovirus infection (P = 0.030), and triglycerides (P = 0.034) were shown to be independent predictors of posttransplant IR. CONCLUSIONS - The OGTT-derived ISITX may be a useful estimate of IS in Caucasian renal transplant recipients, Increasing daily prednisolone dose is an independent predictor of IR after renal transplantation. Hypertension and the use of <beta>-blockers and diuretics may also deteriorate IR in this group of patients.