The isoforms of adenylyl cyclase that mediate cyclic AMP signaling pathways in the retina are, for the most part, unknown. Therefore, the protein expression patterns of adenylyl cyclase isoforms in the rodent retina were characterized immunocytochemically using antibodies directed against Ca(2+)-stimulated (AC1, AC3 and AC8), Ca(2+)-inhibited (AC9) and Ca(2+)-insensitive (AC2, AC4, AC7) isoforms of adenylyl cyclase. The ganglion cell layer and the inner nuclear layer (INL) were immunoreactive for both Ca(2+)-sensitive (AC1, AC3) and Ca(2+)-insensitive (AC2, AC4) isoforms of adenylyl cyclase. Antibodies against isoforms from all three classes of adenylyl cyclase labeled the inner plexiform layer. In the outer retina, antibodies against Ca(2+)-insensitive isoforms labeled photoreceptors and the outer plexiform layer (OPL). Radial elements in the ONL and INL were AC4-immunoreactive and the nerve fibre layer and optic nerve were AC2-, AC4- and AC9-immunoreactive. Antibodies against AC7 did not label rodent neural retina. These data indicate that there is a heterogeneous distribution of adenylyl cyclase isoforms throughout the rodent retina. Nonetheless, there is a general indication of a greater expression of Ca(2+)-insensitive adenylyl cyclase isoforms in the outer retina, particularly within photoreceptors.