Immunocytochemical methods were used to localize type II Ca2+/calmodulin-dependent protein kinase in the macaque primary visual cortex. Neurons that stain for the kinase include both pyramidal and nonpyramidal cells and they appear to form a subset of cortical neurons. They are densely packed in layers II and IVB, somewhat more sparse in layers III, IVC beta, and VI, and nearly absent in layer V. In normal animals the distribution of kinase-positive cells within each layer is relatively uniform. However, in animals in which one eye is removed 7-14 days before sacrifice or sutured shut for 9 or 11 weeks, the cells in layer IVC beta are divided into alternating lightly and darkly stained bands. Comparison of immunocytochemically stained sections with adjacent sections stained for the mitochondrial enzyme, cytochrome oxidase, reveals that the kinase staining increases in ocular dominance columns originally driven by the removed or closed eye. These findings suggest that either the concentration of type II Ca2+/calmodulin-dependent protein kinase or its accessibility to the antibody probe increases dramatically and selectively in neurons of macaque primary visual cortex that have been deprived of their normal visual input. This may indicate that changing levels of activity in cortical neurons can alter their regulatory machinery.