C-peptide secretion was studied in eight juvenile diabetics during the remission phase of the disease. The release of C-peptide was measured after a (1) normal intravenous glucose tolerance test, (2) a double glucose tolerance test, (3) an arginine infusion, and (4) after an intravenous glucose tolerance test followed by an arginine infusion. Under all conditions the intravenous glucose load had only a minimal effect on the secretion of C-peptide, while arginine alone or after the intravenous glucose tolerance test stimulated the release of the peptide in all patients. Pretreatment with glucose did not augment the effect of arginine on C-peptide release. The results indicate that during the remission phase of juvenile-onset diabetes the endocrine pancreas does not recognize glucose as and appropriate signal for C-peptide release and cannot transform the amplifying effect of glucose into a higher hormonal secretion rate.