The present study was undertaken to compare the changes in islet cell antibodies (ICA), islet cell surface antibodies using rat insulinoma cells (RINr-ICSA), and anti-bovine serum albumin antibodies (BSA-Ab) in the clinical course of type 1 (insulin-dependent) diabetes. Sera were obtained from 57 patients with type 1 diabetes and 47 normal controls. ICA, RINr-ICSA and BSA-Ab were detected by an enzymatic immunohistochemical method, an indirect immunofluorescence method and an enzyme-linked immunosorbent assay, respectively. The incidence of ICA significantly decreased with the duration of diabetes: < 1 year: 5 6 (83%); 1-2 years: 3 6 (50%); 2-3 years; 2 6 (33%); >3 years 6 39 (15%). On the other hand, RINr-ICSA and BSA-Ab showed no correlation with the duration of diabetes. There was a significant positive correlation between RINr-ICSA and BSA-Ab (P < 0.05). These findings suggest that RINr-ICSA or BSA-Ab may be produced by some similar immune mechanism which is, however, different from ICA, and that they have no direct relation to the clinical course of diabetes. © 1990.