The newly synthesized human alpha-atrial natriuretic peptide(alpha-hANP)(molecular weight 3082.6) was injected intravenously at stepwise increasing doses of 10, 40 and 75 micrograms into eight normal subjects (mean age +/- s.d. 24 +/- 1 years). The highest dose decreased blood pressure (BP) only slightly under basal conditions (from 118/76 +/- 8/10 to 111/71 +/- 10/13 mmHg, P < 0.005 for systolic BP) and insignificantly during angiotensin II (ANG II) pressor infusion (from 134/98 +/- 9/10 to 137/93 +/- 12/14 mmHg). In contrast, during a noradrenaline (NA) pressor infusion, BP was lowered progressively by the three alpha-hANP doses from 163/96 +/- 12/11 to 156/88 +/- 9/11 (P < 0.02), 148/78 +/- 12/7 (P < 0.001) and 148/70 +/- 10/13 mmHg (P < 0.001), respectively. Heart rate was increased similarly (P < 0.001) by a alpha-hANP during (from 51 +/- 10 to 63 +/- 12 beats/min) or ANG II infusion (from 53 +/- 5 to 64 +/- 10 beats/min). Effects were maximal from 1 to 4 min, lasting for 10 min. These observations reveal that alpha-hANP possesses vasoactive properties independent of a natriuretic action in normal subjects. Alpha-atrial natriuretic peptide may interact preferentially with noradrenergic as compared with angiotensinergic blood pressure control mechanisms.