We have done a study designed to ascertain the effectiveness of measuring antibodies to glutamic acid decarboxylase (anti-GAD) in predicting insulin-dependent diabetes mellitus (IDDM). Anti-GAD was measured in prediabetic sera from 151 women aged 20-39 years with newly diagnosed diabetes mellitus who had been identified through a nationwide diabetes register. Multiple serum samples had been collected from these women up to 10 years before the clinical onset of diabetes during their earlier pregnancies. Anti-GAD was measured with a radioimmunoprecipitation assay. Anti-GAD was detected in 82% of 28 women with IDDM, in 36% of 11 women with non-insulin-dependent diabetes mellitus, and in 5% of 112 women with gestational diabetes mellitus. In a random sample of 100 non-diabetic young Finnish women, none had anti-GAD. The sensitivity of the anti-GAD assay for predicting IDDM was 82.1% and the specificity was 100%. The longest time of anti-GAD positivity before clinical onset of IDDM was 10 years. Once positive, anti-GAD levels remained stable and no patients became negative after a positive test during the prediabetic period. Anti-GAD is a valuable early predictive marker and is associated with a very high risk for development of IDDM.