OBJECTIVESWe derived smooth muscle cells (SMCs) from lung terminal parenchyma and studied the effect of high altitude hypoxia (HAH) on their monolayer morphology and growth profiles.METHODSLungs were obtained from adult sheep kept at 12, 470 ft altitude, PaO2 ~60 Torr for ~4 months and age matched control sheep kept at sea level. SMCs migrated from terminal lung parenchyma were cultured as monolayers, characterized by alpha‐smooth muscle actin immunofluorescence, and studied for monolayer morphologies and tritiated (3H) thymidine incorporation growth profiles.RESULTSHAH‐SMC morphologic varieties were: apoptotic, sub‐confluent, spindle‐form, hill and valley, swirl‐form, and rhomboid monolayers and control SMC varieties were swirl and hill‐and‐valley formations at confluence, jointly from vascular and bronchiolar termini. The normal growth pattern, typified by intrapulmonary 7th generation vein SMCs, showed mean peak 3H‐thymidine incorporation of 2829.46±294.24 counts per minute (cpm) at 72h. Comparatively, HAH‐SMCs profiles were varied: normal, subprolific, prolific, retarded, and senescent. At extremes, mean peak cpm by prolific cells were 7775.42±475.77 and by senescent cells were 26.71.CONCLUSIONChronic HAH caused morphologic and functional changes, possibly combined pathologic formations and adaptive responses, in juxta‐alveolar SMCs.NHLBI MIRS HL‐059435 to T. A. John