We describe a sensitive, simplified radioimmunoassay method for determination of plasma renin activity. Plasma was acidified to the optimal pH (6.0) of angiotensin l generation with the least possible dilution, by using a single addition of hydrochloric acid and the enzyme inhibitor hydroxyquinoline. Recovery of unlabeled angiotensin l added to plasma was 92-97%; that of monoiodinated angiotensin l exceeded 90%, indicating satisfactory protection from proteolytic enzymes. Plasma constituents interfered little with the radioimmunoassay. Bland values for plasma kept at 0 degrees C were 10.7 +/- 2.3 (mean +/- SD) percent of the activity values for samples kept at +37 degrees C (n equals 63). In the routine setting, 6.25 pg of angiotensin l or 10(-6) Goldblatt units of Standard Human Renin was detected. We report results of plasma renin activity measurements and a comparison with seven renin kits, and with bioassay for plasma renin activity.