The decrease in lung angiotensin converting enzyme (ACE) activity occurring in rats during chronic hypoxia might be related to the pulmonary haemodynamic response or to the hypoxia. A study in rats was carried out to investigate this question. Rats from the Hilltop (H) strain are known to develop more severe pulmonary hypertension as a result of chronic hypoxia than rats from the Madison (M) strain despite having virtually identical arterial and mixed venous oxygen tensions. Rats from H and M strains were exposed to hypoxia (0.5 atm) for 3-21 days and lung and serum ACE activities were determined. After three days' hypobaria lung ACE activity was significantly lower and serum ACE significantly higher in H than in M rats. Linear regressions for lung ACE activity and right ventricular:body weight ratios showed significant inverse correlations and were similar in the two strains. The results suggest that pulmonary hypertension and not hypoxia determines the reduction in lung ACE activity, possibly by releasing ACE into the blood stream.