SummaryHigh concentrations of immunoreactive trypsin (IRT) in the blood, and low concentrations of trypsin activity in fecal specimens have been found in newborn infants with cystic fibrosis (CF). The amniotic fluid concentrations of IRT and of IRT in complex with &agr;1‐antitrypsin (&agr;1AT) were studied in 39 samples taken in about the 17th gestational week, and in 7 samples taken because the mothers had previously given birth to children with CF. The midtrimester samples contained trypsin in complex with &agr;1AT in a concentration of 30‐200 &mgr;g/liter, and small amounts of trypsinogen, 0‐50 &mgr;g/liter. Three of four amniotic fluid samples from CF fetuses had very low concentrations of trypsin in complex with &agr;1AT (<10 &mgr;g/liter), and only small amounts of trypsinogen (<10 &mgr;g/liter). Further prospective studies are needed to ascertain whether the determination of IRT in amniotic fluid may be of use in prenatal diagnosis of CF.Abbreviations&agr;1AT, &agr;1‐antitrypsinCF, cystic fibrosisg.w., gestational weekIRT, immunoreactive trypsinRIA, radioimmunoassay