Cyclic GMP(cGMP) in the duodenal contents of 12 normal subjects, 16 patients with chronic pancreatitis, 6 with acute pancreatitis, 5 with pancreatic cancer, 12 suspected of having chronic pancreatitis and 5 with cholelithiasis were measured after a single dose of pancreozymin and secretin. In several patients the plasma level of cyclic nucleotides was measured. Cyclic GMP output was increased, but not significantly, by stimulation with pancreozymin and secretin. No significant difference between the normal and any of the pancreatic disease groups was observed in duodenal cGMP output after secretin administration. The participation of cGMP in human pancreatic secretion could not be comfirmed. Cyclic AMP(cAMP) and cGMP were determined to be secreted by different systems. Plasma cAMP level in the liver disease patients was higher than that in normal subjects before stimulation and increased more after stimulation.