We have recently reported that the AF concentrations of surfactant protein A (SP-A) and saturated phosphatidylcholine (Sat PC) are decreased in fetuses with CDH (Am J Ob Gyn 173:1401, 1995). Nonetheless, it is still unclear if these abnormalities correlate with outcome and whether other fetal lung proteins are also decreased in AF in the presence of CDH. In this study we measured SP-A by ELISA, Sat PC by thin layer chromatography after exposure to osmium tetroxide, as well as surfactant protein B (SP-B) and clara cell protein (CCP) using Western blotting and RIA, respectively, in AF samples obtained by amniocentesis from a group of fetuses with CDH diagnosed by prenatal ultrasound (n=27, GA 16-41 wks), and compared them with measurements from a control population of normal fetuses (n=95, GA 14-41 wks). In the control group there were progressive increases in SP-A (R=0.53, p<0.00001), Sat PC (R=0.59, p<0.00001) and CCP (R=0.43, p<0.00001) with advancing gestation. Comparisons between both groups were done by ANCOVA using gestational age as covariate. The AF concentrations of SP-A (F=9.55, p=0.002), Sat PC (F=14.44, p=0.0002) and CCP (F=13.77, p=0.0003) were significantly lower in fetuses with CDH than in controls. However, the AF concentration of total SP-B of controls (n=35, GA 30-41 wks) was quite variable and was not different from fetuses with CDH (n=20, F=2.33, p=0.13). Also, no differences were found in the AF concentration of mature SP-B (8 KD) or its 26 KD and 42 KD precursors. Using discriminant analysis or multiple logistic regression to determine the outcome of fetuses with CDH, CCP in AF correctly predicted survival vs death or need for ECMO in 80% of cases (sens. 56%, spec. 94%) compared with 76% of cases for SP-A and Sat PC (sens. 56%, spec. 88%). Using a combination of these measurements plus GA did not improve their predictive ability. These findings suggest that the AF concentration of several fetal lung products are markedly decreased in AF from pregnancies with fetuses with CDH, and that these abnormalities exhibit some correlation with outcome in this population.