The aim of the present study was to isolate and identify proteins involved in the process of spermatogenesis. To achieve this goal we used the technique of proteomic analysis. Comparison of testis protein patterns obtained by high-resolution two-dimensional gel electrophoresis from 1-week- and 7-week-old mice showed significant differences in protein spot intensities. Subsequently several of these variant protein spots were identified by mass spectrometry. Glucose-regulated protein (GRP) 78 (Bip) was one of them. GRP78, expressed at a lower level in 1-week-old mouse testes compared to 7-week-old mouse testes, is a member of the heat shock 70 protein family. It has recently been shown to be important for protecting cells from apoptosis in somatic cells, especially in progressively growing tumor cells. Further, immunohistochemical (IHC) analyses of mouse and human testes sections were performed to determine the cellular distribution of this protein. A strong GRP78 staining was seen beginning with pachytene spermatocytes. These findings suggested that GRP78 might perform an important function in the process of spermatogenesis.