The presence of an intrinsic inhibitor of ACE in blood of approximately 25% of sera submitted for serum ACE assay in the diagnosis and evaluation of patients with sarcoidosis, and the common use of ACE inhibitors (captopril and enalapril) in the treatment of hypertension and congestive heart failure, stimulated these studies to compare the effects of the intrinsic and medicinal inhibitors upon serum ACE activity. Since the intrinsic ACE inhibitor in man is affected by serum dilution (inhibition is reversed) and by dialysis (inhibition becomes irreversible), these manipulations were also studied with medicinal inhibitors to provide guidelines for suspecting their presence in submitted serum samples without an accompanying history. Enalapril was found to have delayed onset of action after oral administration (1-2 hours), and was even further delayed (4 hours) when the intrinsic inhibitor also happened to be present. Inhibition by enalapril was not attenuated with refrigerated storage, with dilution or with dialysis of the serum. Captopril had a more rapid time of onset of ACE inhibition, but its inhibitory activity was markedly reduced with refrigerated storage of the serum; patients showed either a short half-life for the effect (1-4 days) or a prolonged half-life (10-17 days). Inhibitory activity of captopril was reversed following dilution of serum or following dialysis. The reversal of inhibition by captopril following dialysis, therefore, differed from the effect of dialysis on the intrinsic ACE inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)