Previous alveolar epithelial cell culture studies have shown that both the amiloride-sensitive epithelial sodium channel (ENaC) activity and its mRNA can be down regulated by protein kinase C (PKC) (1) The aim of this work was to determine whether or not PKC activation can reduce the net lung liquid absorption rate (J_v) in adult rat lungs. Male Wistar rats were anaesthetised using a solution of 25% Hypnorm (Fentanyl Citrate & Fluasinone), 25% Hypnovel (Midazolam) and 50% water (2.7 ml/kg i.p). The rat was ventilated with room air then a median sternotomy was performed and the pulmonary artery and left atrium were catheterised. The lungs were perfused with a modified Ringer’s solution containing 3% albumin. 15ml/kg body weight of liquid, containing an impermanent tracer (Blue Dextran), was instilled into the lung lumen. The lung liquid (LL) volume was calculated by measuring absorbance of LL samples at 620nm. LL volume was plotted against time to calculate J_v. The PKC activator phorbol-12-myristate-13-acetate (PMA 0.1μM) was instilled into the LL after a control period. This resulted in no significant change in the J_v (p= 0.87). However, when a calcium ionophore, ionomycin (1μM) was given in conjunction with PMA, Jv was reduced from -0.0262 ± 0.003 ml/min/g dry lung weight (mean ± S.E.M.) to -0.005 ± 0.006 ml/min/g dry lung weight (p= 0.03; Figure 1). The reduction in J_v caused by PMA and ionomycin was blocked by the PKC inhibitor chelerythrine chloride (1μM), -0.025 ± 0.004 ml/min/g dry lung weight to -0.025 ± 0.001 ml/min/g dry lung weight (p= 0.933; Figure 1). This result was confirmed when a different PKC inhibitor GF109203X was used (0.1μM) p= 0.521. From results obtained it appears that PKC does indeed regulate lung liquid absorption. The use of a PMA in conjunction with ionomycin suggests that the PMA is acting on the calcium dependent isoenzyme (c)PKC. This reduction in J_v was blocked using two separate PKC inhibitors suggesting that the mechanism is most likely PKC dependant.