Aberrant phosphorylation of tau is linked to formation of the paired helical filaments (PHF) seen in Alzheimer's disease. Protein kinases such as mitogen-activated protein kinase, and calcium-regulated protein kinases may, in part, be responsible for addition of phosphate groups to serine residues of PHFtau; however, less is known concerning the phosphatases which regulate tau. In this report, we used several well-characterized antibodies to document calcineurin immunoreactivity in brain tissue from patients with Alzheimer's disease. We now report that levels of immunoreactive calcineurin are not significantly altered in neocortex and cerebellum of Alzheimer's patients relative to similar regions of age-matched controls. Immunocytochemical studies indicated that calcineurin immunoreactivity was present in dendrites and perikarya of many different neuronal populations in both control and Alzheimer brain. When specific antibodies against PHFtau were used in double-labeling experiments with anti-calcineurin antibodies, calcineurin immunoreactivity was seen in association with neurofibrillary tangles. However, calcineurin was not seen in all tangle bearing neurons. These data suggest that calcineurin levels per se are not significantly altered in Alzheimer's disease, but that calcineurin is distributed around some neurofibrillary tangles and may play a role in regulation of tau phosphorylation.