The enzymatic activity of adenylyl cyclase (AC) is attributable to nine isoforms with individual pharmacology and tissue distribution. Polyclonal antibodies for AC isoforms I-IV, VII and VIII were applied to sections of cochlear lateral wall, a tissue involved in ion transport contributing to the unique ion content of endolymph and electrical potential of scala media. Within the stria vascularis, immunoreactivity primarily to Ca 2 + /calmodulin-independent isoforms II, IV and VII was localized to sites consistent in position to the basolateral extensions of marginal cells. Little immunoreactivity was observed in the stria vascularis for Ca 2 + /calmodulin-dependent isoforms I, III and VIII. Within the spiral ligament, type II and type IV fibrocytes exhibited moderate staining for ACII, IV and VII, less staining for VIII and little for I and III. Immunoreactivity to ACII, IV, VII and VIII was observed in type I fibrocytes. The outer sulcus cells and root processes were highly immunoreactive for isoforms I and VIII, but not for III or the Ca 2 + /calmodulin-independent isoforms. The differential pattern of immunoreactivity in the lateral wall overall appears to reflect subfamily-specific expression with Ca 2 + /calmodulin-independent isoforms expressed in the stria vascularis and Ca 2 + /calmodulin-dependent isoforms expressed in the outer sulcus cells and root processes. cAMP-mediated modulation of ion transport by marginal cells is predicted to exhibit, in the microenvironment of basolateral membrane infoldings, pharmacological characteristics of the AC type II subfamily (II, IV and VII), including activation by protein kinase C (II and VII).