At present, the best available estimators of beta-cell mass in humans are those based upon measurement of insulin levels or appearance rates in the circulation. In several animal models, these estimators have been validated against beta-cell mass in lean animals. However, since many diabetic humans are obese, a correlation between in vivo tests and beta-cell mass must be evaluated over a range of body weights to include different levels of insulin sensitivity. For this purpose obese (n=10) and lean (n=25) Gottingen minipigs were studied. Beta-cell mass had been reduced (n=16 lean and n=5 obese) with a combination of nicotinamide (67mg/kg) and streptozotocin (125mg/kg), insulin response (AIR) to iv glucose and/or arginine was tested, pulsatile insulin secretion was evaluated by deconvolution (n=30) and beta-cell mass was determined histologically. AIR to 0.3 (r²=0.4502, p<0.0001) or 0.6 g/kg glucose (r²=0.6806, p<0.0001), 67 mg/kg arginine (r²=0.5730, p<0.001) and maximum insulin concentration (r²=0.7726, p<0.0001) were all correlated to beta-cell mass when evaluated across study groups and regression lines were not different between lean and obese groups, except for AIR to 0.3 g/kg glucose. Baseline pulse mass was not significantly correlated to beta-cell mass across the study groups (r²=0.1036, ns) whereas entrained pulse mass did show a correlation across groups (r²=0.4049, p<0.001). This study supports the use of in vivo tests of insulin responses to evaluate beta-cell mass over a range of body weights in the minipig. Extensive stimulation of insulin secretion by a combination of glucose and arginine seems to give the best correlation to beta-cell mass.