In 15 male patients 45 to 74 yr of age, we measured angiotensin-converting enzyme (ACE) activity during and after cardiopulmonary bypass (all values were corrected for hemodilution occurring during surgery). Baseline ACE measurements (prior to onset of bypass) were 17.6 +/- 6.7 nmol of hippuric acid formed/min/ml (mean +/- SD). After the lung was isolated, serum ACE activity fell rapidly (half-clearance time, 39.5 min) and after 20 min during bypass reached a new steady state 33% below baseline values. Within 10 min of lung reperfusion, serum ACE rose to 90% of baseline values. ACE activity fell (half-clearance time, 198.3 min) and was again significantly below baseline for the period from 60 to 300 min after the end of cardiopulmonary bypass. Serum ACE activity had again returned to baseline when assessed 24 h after surgery; ACE activity in serum fluctuates rapidly, and it is rapidly cleared from serum at a site distant from the lung, probably the liver. Secretion of ACE into the vascular compartment by the lung is impaired in the period immediately after cardiopulmonary bypass.