Soluble guanylyl cyclase is a heterodimeric (alpha,beta) enzyme generating the second messenger, cGMP, upon activation by the gaseous messenger, nitric oxide. The occurrence and distribution of alpha(1)-, alpha(2)-, beta(1)- and beta(2)-subunits were investigated in trigeminal and dorsal root ganglia on the mRNA and the protein level. Reverse transcription PCR analysis demonstrated mRNA coding for alpha(1)-, alpha(2)-, and beta(1)-subunits in guinea-pig trigeminal and dorsal root ganglia. In agreement with these data, immunoreactivity to the alpha(1)-subunit was found in satellite and Schwann cells, while alpha(2)-subunit immunoreactivity was localized to axons of large diameter. The distribution of the beta(1)-subunit could not be studied on the protein level since the antiserum was ineffective in immunohistochemistry. However, previous studies and the RT-PCR data argue in favour of alpha(1)/beta(1)- and alpha(2)/beta(1)-heterodimerization and colocalization. In both species, beta(2)-subunit immunoreactivity was confined to neuronal perikarya, primarily of large diameter. Although these results were obtained with two different antibodies directed against different epitopes, the corresponding mRNA could not be detected by RT-PCR analysis. The reason for this discrepancy remains unclear, at present, but could be explained by a variant beta(2)- or highly homologous as yet unidentified beta-subunit. This study demonstrates the presence of soluble guanylyl cyclase in sensory ganglia with a differential, cell type-specific distribution of the individual subunits.