An immunoassay based on monoclonal antibodies with specificity for the three major isoenzymes of alkaline phosphatase (ALP) has been used in second-trimester prenatal diagnosis of cystic fibrosis (CF). 140 pregnancies with a 1-in-4 risk of CF were assessed prospectively, and outcomes are reported for 100 of these. In 9 cases the diagnosis could not be confirmed or excluded, in 65 cases the infant was normal, and in 15 the infant had CF. In the remaining 11 cases, in which the pregnancy was terminated, the diagnosis of CF was confirmed in the abortus by measurement of albumin and protease levels in meconium scraped from the fetal ileum. Of the 26 cases of CF in the prospective series, 23 (88%) had values of intestinal ALP below half the median value for the corresponding week of gestation. Among those with normal outcomes 3 of 65 (4.6%) were below half-median. When prospective and retrospective data are summed the sensitivity of the test was 91% (39 of 43) and the false-positive rate 6% (5 of 81). This is probably an acceptable form of prenatal diagnosis of CF for the high-risk mother.