To elucidate the clinical significance of antibodies to glutamic acid decarboxylase (GAD Ab) compared to islet cell antibodies (ICA) in recent-onset and long-standing insulin-dependent diabetes mellitus (IDDM). We examined GAD Ab and ICA in 29 recent-onset and 85 long-standing patients with IDDM. GAD Ab was detected by a radioimmunoassay kit using purified pig brain GAD as an antigen. The prevalence of GAD Ab in the recent-onset diabetic patients was 55.2%, slightly lower than that of ICA (65.5%). In contrast, the prevalence of GAD Ab in long-standing diabetic patients was 42.4%, which was significantly higher than that of ICA (23.5%) (p < 0.01). GAD Ab were consistently detected in approximately 40% of patients with long-standing disease, while ICA decreased according to duration of disease. The GAD Ab titer in ICA-positive patients (mean +/- SD, 1588.2 +/- 6755.1; range, 6-38574) was significantly higher than that in ICA-negative patients (mean +/- SD, 13.4 +/- 17.9; and range, 5-72 units) (p < 0.001). These findings suggest that GAD Ab are more useful than ICA to know participation of immune disorders in long-standing patients with IDDM.