We investigated the effect of sodium chloride and adrenergic agents on the release of atrial natriuretic factor (ANF) using working heart-lung preparations from Dahl salt-hypertension sensitive (S) and Dahl salt-hypertension resistant (R) rats. High concentrations of NaCl moderately increased ANF release, but this was attributed to small increases in left atrial pressure rather than to a direct effect of NaCl on ANF release; S and R rats responded similarly. Neither isoproterenol (beta 1 + beta 2 agonist) nor clonidine (alpha 2 agonist) had any effect on ANF release in the heart-lung preparation. In contrast, phenylephrine (alpha 1 agonist) stimulated ANF release. This could not be accounted for by change in atrial pressure and appeared to be a direct effect. S and R rats both released ANF in response to phenylephrine, but there was a modest tendency for hypertensive S rats to release more ANF than normotensive R rats, which is consistent with previous data on mechanically induced (atrial stretch) ANF release in these strains.