Parameters determining glucose tolerance were quantified with Bergman's minimal-model method applied to frequently sampled intravenous glucose tolerance tests in five normal and five islet-autotransplanted mongrel dogs 8-10 mo posttransplantation. Despite normal fasting glucose and insulin levels, glucose tolerance was reduced in the islet-transplanted dogs (1.5 +/- 0.4 vs. 4.2 +/- 0.4%/min in normal controls, P less than .002). The reduction in glucose tolerance was due to a reduced insulin response to glucose injection (4 +/- 1 vs. 32 +/- 5 microU/ml, P less than .001) and reduced glucose effectiveness (1.7 +/- 0.5 vs. 5.3 +/- 0.6 x 10(2) min-1, P less than .005) but not to a reduction in insulin sensitivity (8.4 +/- 0.6 vs. 7.8 +/- 0.7 x 10(4) min-1.microU-1.ml-1, P greater than .5). Our results suggest that reduced insulin secretory response as a result of islet transplantation may result in a defect in glucose's ability to promote its own disposal but not necessarily in a defect in insulin sensitivity.