Sera from 114 first-degree relatives of insulin-dependent diabetes mellitus (type I diabetes) patients and 81 healthy individuals living in Germany were analyzed for antibodies to rat brain glutamic acid decarboxylase (GAD-ab) using an immunoprecipitation assay. The determination of GAD-ab in the 81 islet cell antibody (ICA) and insulin autoantibody (IAA) negative healthy individuals established a normal range (mean +/- 2 SD); 2 healthy individuals (2.5%) possessed GAD-ab levels above this range, but became negative on follow-up. None of 86 ICA-/IAA- first-degree relatives had GAD-ab; whereas, 42.9% of 28 ICA+ and/or IAA+ relatives were positive for GAD-ab. Presence of GAD-ab was negatively correlated with IAA (P = 0.02) and positively with ICA (P = 0.0006). Follow-up samples were obtained from 25 of 28 ICA+ and/or IAA+ relatives with a mean (+/- SD) follow-up period of 20.6 +/- 12.1 months. In these 25 relatives, GAD-ab were positive in 70% ICA+/IAA-, 0% ICA-/IAA+, and 57.1% ICA+/IAA+ relatives in the first sample and in 57.1% ICA+/IAA-, 0% ICA-/IAA+, and 70% ICA+/IAA+ relatives in the last sample. GAD-ab, once detected, persisted in 9 of 11 GAD-ab+ relatives. Of the relatives, 2 converted to GAD-positivity, concomitant with the appearance of ICA, and 2 others lost GAD-ab during follow-up. Of the 28 ICA+ and/or IAA+ relatives, 6 progressed to overt type I diabetes on follow-up, and GAD-ab were detectable in 4 of these relatives.(ABSTRACT TRUNCATED AT 250 WORDS)