Porphyrin- and endogenous peroxidase-containing accumulations of cytoplasmic inclusions in astrocytes of the hypothalamic periventricular and arcuate nuclei and periventricular areas of the lateral ventricles except for ependymal astrocytes were observed by fluorescent microscopy and histochemical techniques in the wild type, C57BL/6J, and tabby mice. These cells can be also visualized with phase contrast and dark-field techniques or by staining sections embedded in polymerized resin with toluidine blue. The brains of heterozygous females and hemizygous males for the blotchy allele (mottled locus on the X-chromosome) failed to show this specific class astrocytes. The findings described are possibly due to defective copper metabolism in mottled mutants which may include a number of other related abnormalities, including reduced activity of copper-dependent enzymes such as porphyrin-containing peroxidases. Sexual differnce in the number of the accumulations in the anatomically and physiologically normal tabby mouse was clearly expressed.