SummaryBackground Impaired glucose tolerance (IGT) and diabetes mellitus (DM) occur more frequently after bone marrow transplantation and total body irradiation (BMT/TBI), but the mechanism is unclear. This study investigates insulin sensitivity, b-cell reserve and pancreatic volume in adult survivors of childhood acute lymphoblastic leukaemia (ALL). Method Survivors (aged 16-26 years) of ALL treated with BMT/TBI (10-14Á4 Gy) Group 1 (n = 20, 10 M) were compared with a chemotherapy-only Group 2 (n = 28, 11 M). Participants underwent assessments of insulin sensitivity by whole body composite-insulin-sensitivity-index (ISI comp ) from oral glucose tolerance tests (OGTTs); first (AIR arg , AIR g , AUC in10 ) and second (AUC in second phase ) phase insulin responses from arginine-intravenous glucose tolerance tests; and pancreatic volume by abdominal magnetic resonance imaging (MRI). Data were analysed by odds ratio, Chi-square or Fisher's exact tests, Student's t-tests, analysis of covariance (ANCOVA) and Pearson's or partial correlations (5% significance). Results Abnormal OGTTs were documented in Group 1 (DM = 2, IGT = 7). Insulin secretion adjusted for insulin sensitivity was lower in Group 1 than Group 2 as a whole [LogAIR arg (P = 0Á008), logAIR g (P = 0Á013) and logAUC in10 (P = 0Á014)] and after exclusion of those with abnormal glucose tolerance [logAIR arg (P = 0Á011), logAIR g (P = 0Á007) and logAUC in10 (P = 0Á006)]. Group 1 had lower pancreatic volume than Group 2 [52Á0 (14Á2) vs 72Á8 (23Á5), P = 0Á001] cm 3 , and results were