The aim of this study was to investigate the relationship of metabolic control to insulinogenic reserve in insulin-dependent diabetics. Thus, the secretory reserve of the pancreatic beta cell was estimated in insulin-dependent diabetics by measuring changes in peripheral serum immunoreactive C-peptide (IRCP) concentrations in response to intravenous arginine (n = 19; 0.5 g/kg, t = 30 min) or glibenclamide-glucose (n = 6; 2 mg HB 419-0.33 g/kg intravenously). In the majority of "stable" diabetics a small secretory reserve of the beta cell was demonstrated, but both the absolute and relative increase in IRCP was reduced after intravenous arginine or glibenclamide-glucose in comparison with normal controls. In "unstable" diabetics a decreased basal concentration of IRCP, significantly smaller than that seen in "stable" diabetics (p less than 0.01), was accompanied by a complete lack of IRCP release on intravenous arginine administration. Thus, we conclude that the radioimmunological determination of IRCP is of clinical interest in assessing the residual secretory capacity of the beta cell in insulin-dependent diabetics. In revealing a lack of insulin this diagnostic tool seems to detect a group of potentially "unstable" diabetics in need of strict observation, which would minimize the risks of bad metabolic control.