The precise functional significance of the inflammatory cells that infiltrate seminomas remains poorly understood. The present study analyzed 15 cases of testicular and extragonadal seminomas (germinomas) by light and electron microscopy, as well as by immunohistochemical methods, with emphasis on the inflammatory cell-tumor cell interaction. Ultrastructurally, in all 15 cases the lymphocytes (mainly consisting of small lymphocytes) were found to be in intimate contact with the intact tumor cells and with those that displayed damage of varying degree. In particular, relatively early damage, such as local loss of the membrane and/or cytoplasm, occurred at the contact regions. Often, the lymphocytes penetrated deeply into the cytoplasm, even into the nucleus of the tumor cell. In spite of the severe damage to the tumor cells, the lymphocytes were themselves intact. The stromal cells contacted by lymphocytes did not show damage. The tumor cells were in contact with epithelioid cells of granulomas in six cases and scattered macrophages in 11 cases showed damage similar to that seen in tumor cells in contact with lymphocytes. The great majority of the lymphocytes were UCHL1-positive cells. L26- or Leu-7-positive cells were rarely found. The epithelioid cells and scattered macrophages were positive for MAC387. The present morphologic study suggests that the infiltrating lymphocytes, epithelioid cells (probably derived from macrophages), and macrophages may be directly cytotoxic to the tumor cells in the microenvironments of testicular and extragonadal seminomas (germinomas).