['Opiate antagonist agents ameliorate pruritus in some patients with cholestatic liver disease, suggesting that endogenous opioids may mediate pruritus in cholestasis. However, the endogenous opioids potentially responsible for pruritus remain unknown. Methionine-enkephalin is an endogenous opioid synthesized in numerous tissues including the gastrointestinal tract, and released into the portal circulation. Serum methionine-enkephalin concentrations are elevated in patients with chronic liver disease, making this opioid a candidate for opioid-mediated pruritus in cholestatic liver disease. The aim of our study was to determine whether elevated circulating methionine-enkephalin concentrations are associated with pruritus.', 'Serum concentrations of methionine-enkephalin were measured in 54 consecutive, untreated patients with primary biliary cirrhosis and 20 healthy controls. There was a direct correlation between methionine-enkephalin concentrations and total serum bilirubin (r = 0.42, p < 0.05) and the Mayo risk score (r = 0.5, p < 0.005). Methionine-enkephalin concentrations were significantly higher in histological stages 3 and 4 (48 +/- 4 pg/ml, n = 44), compared with stages 1 and 2 (29 +/- 12 pg/ml, n = 10, p < 0.05). Methionine-enkephalin concentrations in both histological groups were significantly higher than those in 20 healthy controls (16 +/- 4 pg/ml, p < 0.005).', 'There was no significant correlation between methionine-enkephalin concentrations and the presence of pruritus (46 +/- 25 pg/ml with pruritus vs. 40 +/- 22 pg/ml without pruritus, n = 20).'] Do methionine-enkephalin concentrations correlate with stage of disease but not pruritus in patients with primary biliary cirrhosis?