Newborn calves exposed to hypobaric hypoxia develop severe pulmonary hypertension. Right ventricular hypertrophy and failure occur as a consequence of the increased pressure load. Alterations in right ventricular myocyte performance or differentiation could be reflected by the changes in the expression of contractile protein genes. We studied expression of contractile actin isotypes by measuring mRNA levels in total cellular RNA purified from right (RV) and left ventricles (LV) of calves with severe pulmonary hypertension after a 2-wk exposure to hypobaric hypoxia and age-matched controls. alpha-Skeletal actin mRNA was increased greater than 10-fold in the RV of hypertensive animals, whereas alpha-cardiac actin mRNA did not appear to change. alpha-Skeletal actin mRNA and alpha-cardiac actin mRNA did not increase in the LV of any of the hypoxic animals. After a 2-wk hypoxic exposure, calves were removed from the chamber. Two days later, RV alpha-skeletal actin mRNA decreased dramatically but was apparently elevated above that of an age-matched control. Thirty days after hypoxia, there appeared to be a persistent increase in RV alpha-skeletal actin mRNA. Although the physiological significance of these changes are unknown, an alteration in the RV myocyte phenotype has occurred.