Immunohistochemical studies of pancreatic tissue from patients with cystic fibrosis associated with diabetes mellitus (CFDM) show increased numbers of somatostatin secreting delta cells. To look for a possible functional correlate to this finding basal and arginine stimulated plasma somatostatin and serum C peptide concentrations in eight insulin treated patients with cystic fibrosis and eight normal male controls were measured. Mean basal somatostatin concentrations were not different in the two groups. Mean peak somatostatin concentrations were significantly higher in the group with CFDM: 11.60 pmol/l v 7.14 pmol/l in controls. Mean peak C peptide concentrations were significantly lower in the group with cystic fibrosis: 0.89 nmol/l v 4.27 nmol/l in controls. This observation provides a physiological correlate to the pathological finding of increased somatostatin content in pancreatic tissue from patients with CFDM. Selective preservation of somatostatin secretion in patients with cystic fibrosis may further complicate pancreatic endocrine insufficiencies through paracrine inhibition of insulin and glucagon secretion.