Chloride (Cl⁻) movement across fetal lung epithelia is thought to be mediated by the sodium-potassium-2-Cl⁻ cotransporter NKCC1. We studied the role of NKCC1 in Cl⁻ and liquid secretion in late-gestation NKCC-null ( − / − ) and littermate control fetal mouse lung. NKCC − / − mice had decreased lung water compared with littermate controls (wet/dry: control, 8.01 ± 0.09; NKCC − / − , 7.06 ± 0.14). Liquid secretion by 17-d NKCC − / − distal lung explants was similar to control explants. Bumetanide inhibited basal liquid secretion in control but not NKCC − / − explants (expansion over 48 h: control, 35 ± 4%; NKCC − / − 46 ± 7%). Treatment with 4,4 ′ -diisothiocyanto-stilbene-2,2 ′ -disulfonic acid (DIDS) decreased liquid secretion in both control and NKCC − / − explants. Basal transepithelial potential difference (PD) of control tracheal explants was higher than that of NKCC − / − (control, − 13.7 ± 0.5 mV; NKCC − / − , − 11.6 ± 0.6 mV). Amiloride (10^{− 4} M) inhibited basal PD to the same extent in control and NKCC − / − mice. Terbutaline-stimulated hyperpolarization was less in NKCC − / − than in control tracheas ( Δ PD: control, − 10.8 ± 1.33 mV; NKCC − / − , − 6.1 ± 0.7 mV) and was inhibited by DIDS and acetazolamide in NKCC − / − but not wild-type explants. We conclude that NKCC is rate-limiting for transcellular Cl⁻ transport, and that alternative anion transport mechanisms can sustain liquid production at near-normal levels in the fetal NKCC − / − mouse lung.