Relationships among islet cell antibodies (ICA), residual β-cell function, and metabolic control were studied in 60 insulin-dependent diabetics (IDDs) of long duration (6 to 31 years). Sensitive C-peptide immunoreactivity (CPR) and ICA assays with limits of 0.017 nmol/L and 5 Juvenile Diabetes Foundation (JDF) U, respectively, demonstrated that baseline (0.16 ± 0.02 nmol/L, mean ± SE, n = 26), as well as maximum CPR values (0.34 ± 0.05 nmol/L), during 100-g oral glucose tolerance tests (OGTT) in ICA-positive IDDs were significantly higher than corresponding values in ICA-negative ones (baseline values, 0.10 ± 0.01 nmol/L, P < .05; maximum values, 0.20 ± 0.04 nmol/L, P < .01, n = 34). Negative correlation was observed between increment of serum CPR and metabolic control indices, including fasting blood glucose (FBG) and HbA1c levels (P < .05). In addition, ICA-positive insulin-dependent diabetes mellitus (IDDM) patients had lower values of FBG (8.2 ± 0.4 mmol/L, P < .01 v ICA-negative IDDs) and HbA1c (9.2% ± 0.2%, P < .05 v ICA-negative IDDs) than ICA-negative ones (FBG, 9.9 ± 0.4 mmol/L; HbA1c, 9.8% ± 0.2%). These results indicate that minute CPR responses to OGTT detected by sensitive methods may represent residual pancreatic β cells, which may contribute to ICA generation and good metabolic control in IDDs of long duration. © 1990.