Insulin-dependent diabetes mellitus (IDDM) is a slowly progressive autoimmune disease. In the prediabetic phase of IDDM, the intravenous glucose tolerance test (IVGTT) demonstrates a progressive decline in the first-phase insulin response. The first-phase insulin response to intravenous glucose may enable individuals at risk of IDDM to be identified and preventive therapy to be instituted. However, the reproducibility of the first-phase insulin response is controversial. The aim of this study was to determine the variability of the first-phase insulin response to intravenous glucose. Ten healthy normal volunteers underwent two IVGTT within a 1 week interval, using the Islet Cell Antibody Register User's Study (ICARUS)-recommended standard protocol. The first-phase insulin response to intravenous glucose was expressed as the sum of the 1- and 3-minute insulin concentrations (mu U/mL) and the total 0 to 10 minute insulin area under the curve (mu U . min . mL(-1)). Variability was represented by the coefficient of variation (CV). The within-subject median CV was 21.2% for the sum of the 1- and 3-minute insulin concentrations and 23.9% for the total 0 to 10 minute insulin area under the curve. In conclusion, the reproducibility of the first-phase insulin response to intravenous glucose is poor. Hence, caution should be exercised when the IVGTT is applied to prediabetic IDDM patients for longitudinal study.