Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Adrenomedullin (AM) has diuretic, natriuretic, and hypotensive effects. To study the possible effects of HHE on the AM synthesis system, 150 male Wistar rats were housed in a chamber at the equivalent of the 5500m altitude level for 21 days. After 14 days' exposure to HHE, pulmonary arterial pressure (PAP) was significantly increased (as compared with control rats). The plasma AM protein level was significantly increased on day 21 of exposure to HHE. In the right ventricle (RV), right atrium (RA), and left atrium (LA) of the heart, the expressions of AM mRNA and protein were increased in the middle-to-late phase (5-21 days) of HHE, while in brain and lung they were increased much earlier (0.5-5 days). In situ hybridization and immunohistochemistry showed AM mRNA and protein staining to be more intense in RV in animals in the middle-to-late phase of HHE exposure than in the controls. During HHE, these changes in AM synthesis, which occurred strongly in RV, occurred alongside the increase in PAP. Conceivably, AM may play a role in modulating pulmonary hypertension in HHE.