Immunogiobulin was separated from islet cell antibody positive plasma of six children with newly diagnosed insulin-dependent (type I) diabetes mellitus. The dynamics of insulin release in response to glucose and partially purified antibodies were determined in dispersed rat islet cells perifused on small columns of Biogel P-2 beads. After perifusion at 5.5 mmol/L D-glucose in the presence of healthy control immunoglobulin, the rate of insulin release increased in a biphasic manner after stimulation with 30 mmol/L D-glucose. In cells exposed to diabetic immunoglobulin, 30 mmol/L D-glucose had little, if any, effect on insulin release. These results suggest that islet cell antibodies in insulin-dependent diabetes may interfere with the insulin release mechanisms in the pancreatic B-cells.