Adrenomedullin protected mice with pneumonia against mechanical ventilation-induced lung injury. Pneumococcal pneumonia (S.p.) was induced 24 hours before mechanical ventilation (MV) was performed for 6 hours. Continuous adrenomedullin (AM) infusion (0.05 mg/kg/hour) started with the onset of MV. Nonventilated (NV) mice were sacrificed 30 hours after infection. (A) Human serum albumin (HSA) was injected 90 minutes prior to termination of the experiment and the HSA concentration (cHSA) in plasma and in bronchoalveolar lavage (BAL) was determined. An increased HSA BAL/plasma ratio indicated enhanced lung permeability (*P < 0.05, **P < 0.01; NV, n = 5; NV + S.p., n = 4; MV, n = 5; MV + AM, n = 4; MV + S.p., n = 7; MV + S.p. + AM, n = 5). (B) Peak inspiratory pressure (PIP) was analyzed after 6 hours of MV following a final recruitment maneuver (**P < 0.01; NV and NV + S.p., n = 5; all other groups, n = 8 each). (C) Arterial oxygen partial pressure was determined at the end of the experiment and the P/F ratio was calculated (**P < 0.01; NV and NV + S.p., n = 5; MV, n = 6; MV + AM, n = 7; MV + S.p., n = 5; MV + S.p. + AM, n = 8). (D) In precision cut lung slices, vasoconstriction was induced by hypoxia (hypoxic pulmonary vasoconstriction) and by the thromboxane receptor agonist U46619 in the presence or absence of AM (0.5 μM). The luminal areas of single intra-acinar pulmonary arteries were continuously analyzed by planimetry and the area under the curve (AUC) was calculated for each experiment. Significant AUC differences between the two groups were evident under hypoxia, during the wash out phase and after U46619 challenge (ns, not significant; **P < 0.01, ***P < 0.001; n = 10 each).