We previously reported that IA-2 autoantibodies (Ab) facilitated the diagnosis of Japanese insulin-dependent diabetes mellitus (IDDM), but the number tested was not large enough to investigate whether IA-2Ab can improve the diagnostic accuracy. In this report, sera from 78 patients with less than 2 year-disease duration (the mean (range) ages were 19.2 (6-52) years old) were tested in order to clarify that the combination of IA-2Ab and glutamic acid decarboxylase 65 (GAD65)Ab would improve the test sensitivity for IDDM. Both of the autoantibodies were frequently detected in Japanese abrupt-onset IDDM but the frequency of GAD65Ab was higher than that of IA-2Ab (69% and 47%, respectively, P = 0.024). The two autoantibodies were discordant in respect to both positivity and titer. The positivity for IA-2Ab decreased with the increasing onset-age of the patients (76, 47, 37, 21% for each quartile of age tested), but the frequency of GAD65Ab was unaffected. Among the youngest quartile (< or = 12 years old), IA-2Ab, in combination with GAD65Ab, significantly improved sensitivity (68% to 92%, P < 0.05), but when we tested patients over 12 years old, IA-2Ab caused little, if any, improvement in sensitivity. We confirmed that IA-2 antibody was detected in IDDM among Japanese, as seen in Caucasians, but the test sensitivity was improved only in young IDDM patients among Japanese.