The presence of a peptide resembling atrial natriuretic factor (ANF) was demonstrated in the peripheral sympathetic ganglia of the rat by a sensitive radioimmunoassay. Partially purified ANF-like compounds from the superior cervical ganglia exhibited biological activities which were similar to the synthetic peptide of cardiac origin; they inhibited ACTH-stimulated aldosterone release in vitro and displaced labelled [125I]-ANF from rat adrenocortical cell receptors. The exact source and role of ANF in peripheral nervous structures is not fully understood. We suggest that in sympathetic ganglia ANF may act as a neurotransmitter and/or neuromodulator in a manner similar to other neuropeptides.