The effect of atrial natriuretic factor (ANF) 99-126 3 or 10 pmol/kg/min on increase in plasma renin activity (PRA) stimulated by a 30-min infusion of prostaglandin E2 (PGE2) 80 ng/kg/min was studied in healthy salt-replete male volunteers. PGE2 increased PRA to approximately 230% of basal levels (p less than 0.001). Concomitant infusion of ANF 3 pmol/kg/min significantly attenuated this rise in PRA to approximately 130% of baseline values (p = 0.02, n = 10). A quantitatively similar effect was observed with ANF 10 pmol/kg/min (n = 5). We suggest, in light of previous findings, that this inhibitory effect of ANF probably represents a nonspecific action rather than a specific effect of ANF on PGE2-mediated increases in PRA.