Serum levels of immunoreactive trypsin (TIRS) were determined in 61 children having either alpha 1 antitrypsin deficit, chronic hepatitis, syndromic or non-syndromic ductular hypoplasia, or extrahepatic biliary atresia. Fasting TIRS values in both patients with chronic hepatitis (213 M 81 ng/ml) and with extrahepatic biliary atresia (159 +/- 88 ng/ml) didn't show statistically significant differences in relation to control values (172 +/- 44 ng/ml). However, in children with alpha 1-antitrypsin deficit (518 +/- 275 ng/ml; p less than 0.02) or syndromic (594 +/- 331 ng/ml; p less than 0.01) and non-syndromic ductular hypoplasia (558 +/- 183 ng/ml; p less than 0.02) TIRS levels were significantly above control values. Even more, in these last three groups of patients, their TIRS values were clearly greater than in extrahepatic biliary atresia patients. According to the above findings, we suggest that TIRS values may be a valuable marker for the differential diagnosis between intra and extrahepatic cholestasis.