The immunohistochemical localization of cathepsin D (CD) was demonstrated for the first time in 54 schwannomas (32 intra- and 22 extracranial; 47 benign and 7 malignant) and 5 normal nerve fibers. Granular or vesicular CD-reactive structures were observed in all normal Schwann cells. All tumors contained CD-reactive tumor cells, although the population of CD-reactive tumor cells, the density, intracellular localization, and morphology of CD-reactive structures, and the intensity of CD immunoreactivity varied from case to case, portion to portion, and cell to cell, differing variously from those in normal Schwann cells. The variations were greater in malignant than in benign schwannomas. In mildly degenerate tumor cells, CD immunoreactivity was increased, possibly in response to the increased intracellular degenerate proteins, suggesting that the mechanism of induction of lysosomal proteases preserved in normal cells is not affected by the process of neoplastic transformation. In lesions of severe degeneration or necrosis, CD immunoreactivity was lost in most tumor cells but was strong in macrophages invading the lesions and perivascular regions. CD immunoreactivity was observed at various intensities in tumor cells in the Antoni type A area but not in most tumor cells in the Antoni type B area, suggesting that Antoni type B lesions show degenerative changes. The presence of CD-reactive tumor cells in all tumors examined and strong CD immunoreactivity observed at the invasion front of tumors in some cases of benign or malignant schwannoma suggests the possible role of CD in tumor invasion in some cases.