The purpose of this study was to compare the safety and tolerability of recommended initial doses of fosinopril (FOS) with those of captopril (CAP), in diuretic-treated, salt depleted "high risk" patients with congestive heart failure. Thirty patients were randomized in a double blind fashion to receive a single dose of either FOS 10 mg, CAP 6.25 mg or placebo. CAP produced a significant early and brief fall in BP, while the first-dose hypotensive response with FOS did not differ significantly from placebo. Baseline plasma angiotensin converting enzyme (ACE) activity was similar in all groups. Only CAP showed atl acute and significant fail in plasma ACE activity, whereas FOS and placebo did not change ACE activity. There was no correlation between mean arterial pressure or percentile change in mean arterial pressure and plasma ACE activity. Also no correlation was found between high or low ACE activity level and first dose hypotension. The practical importance of the results are: For patients with congestive heart failure, FOS and CAP have different effects on BP after the first dose, and this effect may be dependent on the plasma ACE activity level. FOS produces ACE inhibition and BP changes similar to placebo so it is the safer choice for the treatment of congestive heart failure.