Immunoreactive trypsin concentration and pancreatic lipase activity were measured in the sera of 33 patients with primary biliary cirrhosis. Immunoreactive trypsin was increased (above the normal range) in 16 (48%) and pancreatic lipase activity in 18 (55%) patients. Both enzymes were increased in 10 (30%) patients. Twenty four patients (73%) had an increase of either one or both enzymes. There was a significant correlation between immunoreactive trypsin and pancreatic lipase activity. This abnormality was not related to treatment with D-penicillamine, the age of the patients, the stage of the disease, or the severity of cholestasis. Thus most patients with primary biliary cirrhosis have increased pancreatic enzyme activity and immunoreactive trypsin concentration in their sera. These data are indicative of damage to the exocrine pancreas. The cause of this damage is as yet unknown.