Current radioimmunoassays do not demonstrate total absence of angiotensin II during converting enzyme inhibition. To assess the meaning of plasma angiotensin II determinations during converting enzyme inhibition, plasma angiotensin I and II levels of normotensive humans during maximal converting enzyme inhibition by single oral doses of CGS 13945, MK 421, or MK 521 were compared with those of anephric rats (18 hr after nephrectomy) after intravenous administration of MK 422 (1 mg/kg). Prior to radioimmunoassay, plasma was extracted with Dowex for angiotensin II and blood extracted with ethanol for angiotensin I. During converting enzyme inhibition, in the 20 normotensive subjects plasma angiotensin II was 6.3 +/- 2.3 pg/ml (mean +/- S.D.) and blood angiotensin I was 65 +/- 59 pg/ml. In the nephrectomized rats, plasma angiotensin II was 8.9 +/- 2.3 pg/ml without converting enzyme inhibitor (n = 15) and 7.6 +/- 2.8 with MK 422 (n = 14), and blood angiotensin I was 9.8 +/- 2.4 pg/ml and 8.2 +/- 0.7, respectively. Dowex extraction of Tris buffer containing no angiotensin II provided blank values ranging from 5.0 to 7.8 pg/ml (n = 5). Thus plasma angiotensin II of normotensive humans treated with converting enzyme inhibitors fell to blank levels even in the presence of markedly elevated plasma angiotensin I. Angiotensin II concentrations in anephric rats with or without converting enzyme inhibition were the same. We therefore conclude that plasma levels of angiotensin II below 8 pg/ml measured after Dowex extraction probably reflect complete converting enzyme inhibition and virtual absence of angiotensin II generation.