An immunocytochemical method was used to localize calcineurin, a calcium-dependent calmodulin-stimulated protein phosphatase, in the primary visual cortex of developing and adult cats. In the adult calcineurin immunoreactivity exhibits a laminar distribution with dense labeling in the upper half of layers II/III and two lightly labeled bands in lower layer IV and in layer VI. Most of the immunoreactive neurons are pyramidal in shape and appear to form a subpopulation of cortical neurons, but non-pyramidal neurons were also labeled, especially during early stages of postnatal development. The distribution pattern of calcineurin immunoreactivity showed developmental changes until at least 3 months of age. The number of calcineurin-positive cells abruptly increased at 3 weeks, and heavily labeled neurons appeared in a well-delineated band in layer IV between 3 and 5 weeks of age. At 6 to 10 weeks, neurons in layers II/III also became strongly immunoreactive. At this developmental stage intensely stained cells were thus distributed throughout layers II to IV. Thereafter, there was a marked decrease in the number of immunoreactive cells in layer IV and beyond 12 weeks the distribution pattern of calcineurin immunoreactivity became similar to that of adult animals. These changes of calcineurin expression show some relation with the inside-out pattern of cortical maturation and with the time course and the laminar selectivity of use-dependent malleability. Therefore, we suggest that calcineurin may be involved in processes of neuronal differentiation and experience-dependent plasticity.