Islet cell surface antibodies (ICSA) were raised by immunization of rabbits with viable neonatal rat pancreatic islet cell suspensions. By absorption with liver powder and spleen cells unspecific cytotoxic components were removable from the sera. Cytotoxic effect of islet cell antiserum against islet cells was indicated by 51Cr-release. In dependence on serum concentration beta-cell damage induced by ICSA-positive serum was detectable by insulin leakage from neonatal rat islets of Langerhans. The immune cytolytic effect of rabbit anti-rat islet cell surface serum was accompanied by morphological alterations of the islet surface structure as revealed by scanning electron microscopy. Pretreatment of pancreatic islets with cytotoxic islet cell antiserum results in an increased insulin leakage even after the removal of the cytotoxic conditions suggesting the persistence of cell membrane lesions. Insulin secretion of islets of Langerhans first exposed to cytotoxic ICSA-positive serum is still stimulated by 15 mmol/1 glucose plus 0.1 mmol/1 3-isobutyl-1-methylxanthine (IBMX) but taking into account the increased insulin leakage the secretory capacity of these islets is significantly diminished.