Measurement of insulin autoantibodies (IAA) with a novel micro radiobinding assay which requires only 20 microl of serum was compared with that in a conventional radiobinding assay which uses 600 microl of serum. IAA were measured with both assays in samples from 94 new onset insulin-dependent diabetes mellitus (IDDM) patients, 97 control subjects. and 48 first degree relatives of IDDM patients selected for having IAA in the conventional radiobinding assay. Overall, 227 (95%) of 239 samples tested were concordant. and IAA levels correlated well (r2 = 0.7) between the two assays. Discordant results were obtained in 7 new onset patients, 4 control subjects, and 1 first degree relative, and these had low IAA levels in the respective assays. Sensitivity and specificity in the new onset IDDM patients and control subjects were 69% and 98% for the micro radiobinding assay and 72% and 98% for the conventional radiobinding assay. The use of the micro radiobinding assay should greatly facilitate islet related antibody screening, particularly in children.