Protein kinase C (PKC)-ε regulates myocardial and lung vascular responses to ischemia and acute hypoxia (Hx) by discrete tissue-specific mechanisms. The activation of PKC-ε protects against acute ischemic injury in the heart, while in the lung we have shown that the loss of PKC-ε limits the magnitude of acute hypoxic pulmonary vasoconstriction. Adaptation of the lung circulation to chronic Hx is a more complex process than these acute responses. The pattern of lung vascular responses to chronic Hx may or may not be predicted by acute hypoxic pulmonary vasoconstriction. Therefore, we hypothesized that the loss of PKC-ε would decrease the contractile and/or structural response of the murine pulmonary circulation to chronic Hx. Adult PKC-ε wild-type (+/+) mice and null (–/–) mice were exposed to normoxia (5,200 feet) or Hx (18,000 feet) for 5 weeks.