Abstract The molecular forms of atrial natriuretic factor were studied in the sympathetic ganglia of the rat. The peptide atrial natriuretic factor was also tested for its ability to induce intracellular changes in ganglionic elements. Chromatographic evaluation of extracted ganglionic atrial natriuretic factor revealed the presence of proatrial natriuretic factor together with lower molecular weight peptides. Atrial natriuretic factor induced a maximal six-fold increase of cGMP accumulation within ganglia in vitro, most probably in principal ganglionic cells. Its effect on cGMP was not mediated by acetylcholine or any other neurotransmitter because it persisted after muscarinic receptor blockade and in a calcium-free medium and was not affected by ganglia decentralization. Thus, atrial natriuretic factor appears to be produced by a structural neural component of ganglia (in preganglionic cholinergic neurons or small intensely fluorescent cells?) and has receptors at sites different from its source. It is suggested that atrial natriuretic factor may be locally involved in the process of neurotransmission and may be yet another peptide neurotransmitter and/or neuromodulator.