The natural history of islet cell antibodies (ICA), using standardized Juvenile Diabetes Foundation (JDF) units, was studied for two years in 64 type 1 (insulin dependent) diabetic patients, aged 7-45 years prospectively from clinical onset. While ICA were present among 44/64 (68.8%) of the newly diagnosed patients, only 9.3% remained positive at 24 months. The only factor which showed significant predictive value for ICA survival was high initial JDF ICA titres: Maximal persistence of ICA was observed in patients with 80 JDF units at diagnosis (100% at 12 and 24 month). This persistence was lower in patients with 40 JDF units at diagnosis (77% at 12 month, 40% at 24 month) and the lowest for patients with 5 JDF at diagnosis (14% at 12 month, 0% at 15 month). 14/20 (70%) of patients negative for the ICA test at diagnosis became positive during follow-up, but always with a low titre (5-10 JDF units) and for a short period (3-6 months). It is concluded that initial titre is the most important variable in predicting the maintenance of ICA during the first two years of clinical type 1 diabetes.