Fetal lung liquid (LL) secretion is essential for normal lung growth but at birth this liquid is absorbed rapidly by the β-adrenergic action of adrenaline which activates ENaC, an amiloride blockable sodium channel on the apical surface of the pulmonary epithelium. Sodium is transported into the interstitium with water and other ions thought to follow passively thus clearing the lung lumen of liquid (Olver et al., 2004). We have previously shown, by using the inhibitor KT5720, that protein kinase A does not appear to be involved in the activation of fetal lung ENaC. To explore the possibility that another kinase is part of the intracellular signalling mechanism between beta receptor stimulation and ENaC activation, we performed experiments investigating the involvement of protein tyrosine kinase (PTK). An in utero fetal sheep model, prepared under general anaesthesia (induction with 5% thiopentone and maintenance with 2% halothane) as previously described (Olver et al., 1986) was used. We measured net fetal LL volume change with an impermeant marker (125I human serum albumin) at rest, in the presence of genistein and after stimulation with adrenaline with and without genistein. Experiments were performed at gestations between 135 and 146 days (term 147 days). Adrenaline was infused intravenously at a set rate of 1μg/min and genistein was administered by dissolving in a small amount of DMSO and instilling into the LL to give a final concentration of about 2.6 mM. Genistein alone caused a gestation dependant inhibition of LL secretion (Figure), presumably by activating ENaC, since the effect is blocked by amiloride. Genistein did not block or inhibit the effect of adrenaline but rather enhanced its effect in causing LL absorption (Table). These results are opposite to those of Niisato et al. (1999) who showed that cAMP stimulated sodium transport is inhibited by genistein in rat fetal distal lung epithelial cells grown in culture. We conclude that PTK may produce an inhibitory effect on ENaC i.e. tending to keep it in the inactive state, although an effect on the fetal LL chloride secretory mechanism has not been excluded yet.