Transient hyperglycemia during acute illness may represent the earliest clinical sign of impaired beta cell function. This study sought to characterize the clinical presentation of patients with stress hyperglycemia and to determine the prevalence of immunologic and endocrinologic markers associated with prediabetes. Thirty-six children were studied. They were referred to us for routine evaluation after an episode of hyperglycemia during severe intercurrent illness. Immunologic markers (insulin autoantibodies and islet cell autoantibodies) and intravenous glucose tolerance test for evaluation of first phase insulin secretion rate were performed in all participants. Islet cell autoantibodies were negative in all patients. In eight patients, the first phase insulin response was below the first percentile (46 microU/ml) at the first determination. Insulin autoantibodies were positive in another three children (> 60 nU/ml). Twelve to sixteen months later, all children were re-evaluated and all had normal results. None of the patients developed diabetes during the study (mean 3.2 years). Our data support the idea that episodes of hyperglycemia during severe illness without additional risk factors are a minimal risk factor, if any, for future development of IDDM.