Edema fluid (EF) increases epithelial Na⁺ transport by rat fetal distal lung epithelia (FDLE) and induces net lung fluid absorption in fetal mouse lung explants (Rafii et al, J.Physiol. 544:537-548, 2002). We now show that EF increases fluid absorption across monolayers of rat FDLE in a dose-dependent manner. To study the role of subunits of the epithelial Na⁺ channel (ENaC) in the phenomena, we cultured explants from the distal lungs of 16 day GA wild type (WT) or , or ENaC knockout or heterozygote (HT) mice. WT explants cultured in media continuously expanded over time as a result of net fluid secretion. In contrast, when explants were exposed to EF for 24 h, net fluid absorption occurred. EF-exposed explants had normal histology but marked changes were seen after Triton X-100 or staurosporine exposure. Transmission electron microscopy showed EF promoted lamellar body formation and abundant surfactant in the explants' lumens. EF-induced changes in explant size were similar in -ENaC knockout, WT and HT littermate fetal lung explants (p>0.05). In contrast, EF's effect was attenuated in and -ENaC knockouts (p<0.05) vs. WT and HT littermate fetal lung explants. EF exposure slightly decreased or had no effect on mRNA levels for -ENaC in various mouse genotypes, but decreased expression of and - ENaC subunit mRNAs (p<0.01) across all genotype groups. We conclude that and , but not , ENaC subunits are essential for EF to exert its maximal effect on net fluid absorption by distal lung epithelia.