Abnormal pancreatic excretion of 5,5-dimethyl-2,4-oxazolidinedione (DMO) was demonstrated in 44 patients with chronic pancreatitis (14 with calcification and 30 without calcification). Pancreatic excretion of DMO in patients with chronic pancreatitis, as well as in normal subjects, depended on plasma DMO concentration and secretory volume. In the postsecretin 60-min period, almost all patients showed a decrease in total DMO output of duodenal aspirate over the observed range of plasma DMO concentration. More than half the patients without calcification gave a discordant pattern between the DMO output and volume, ie, decreased DMO output with normal volume secretion, while most of patients with calcification had low DMO output with decreased volume flow. The data of the pancreozymin-secretin test suggested that chornic pancreatic inflammation was moderate or minimal in patients without calcification and far advanced in those with calcification. From these results the hypothesis was advanced that DMO diffusion into the pancreatic ducts might be primarily impaired in the relatively early stage of chronic pancreatitis, and as the inflammation progressed to the final stage, DMO outflow from the ducts to the duodenum would be disturbed with evolving diffusion impairment of the compound. Total DMO output, when expressed as the output at a level of 10 mg/100 ml of plasma DMO (standard DMO output), was significantly reduced in chronic pancreatitis during a 60-min period after secretin stimulation. DMO in duodenal content, when expressed in terms of maximal concentration ratio of duodenal juice/plasma for the compound (maximal J/P ratio), was significantly low in chronic pancreatitis during the last 40-min period after secretin stimulation. These two parameters can therefore be used as indices of pancreatic excretion of DMO. The present technique may well become an effective diagnostic tool for early detection of chronic pancreatitis.