Abstract: Specific polyclonal antibodies that distinguish the two distinct isoforms of the catalytic subunit of calmodulin-dependent protein phosphatase, calcineurin Aα and Aβ, were prepared, and the distribution of calcineurin Aα and Aβ in rat brain was studied using immunochemical and immunocytochemical techniques. Immunochemical measurement revealed that the regional distributions of the two isoforms differed and that Aα was more abundant than Aβ in the rat brain. The subcellular distribution patterns of both isoforms were similar. Both isoforms were highly enriched in cytosolic fractions, including the synaptosomal cytosol. Immunocytochemical analysis revealed that both Aα and Aβ immunoreactivities differed in regional and cellular localizations. These different patterns of expression suggest that the two isoforms of calcineurin A may each have specific functions in modulating neuronal activity in particular cell types.