The purine metabolites inosine and adenosine selectively increase the catecholamine, but not the acetylcholine production in cultured chick superior cervical ganglion neurons via an as yet unknown intracellular pathway. In order to elucidate some of the molecular events involved in this differential regulation of neurotransmitter production by purines, the SCG neurons were cultured in the presence of cyclic nucleotide analogs and activators of adenylate and guanylate cyclase. Neither 8-bromo-cyclic AMP (8-Br-cAMP), 8-bromo-cyclic GMP (8-Br-cGMP), or forskolin, an activator of adenylate cyclase, could mimic the effect of inosine, i.e. differentially increase catecholamine production. Sodium nitroprusside, an activator of guanylate cyclase, however, has a strong potentiating action on the effect of inosine. The noradrenergic properties of chick sympathetic neurons may thus be differentially modulated by a cGMP-dependent pathway.