A cell culture system that supports the differentiation of male germ cells through meiosis is described. It takes advantage of the properties of a cell line, 15P-1, established from testicular cells of transgenic mice that express the large T protein of polyoma virus in the seminiferous epithelium. This line exhibits features characteristics of Sertoli cells, including transcription of the Wilms' tumor (WT1) and Steel genes. Cells of the 15P-1 type support the meiotic and postmeiotic differentiation in cocultures of diploid premeiotic germ cells into haploid spermatids expressing the protamine (Prm-1) gene. When cocultured with 15P-1 cells, testicular cells explanted from immature 9-day-old animals, before the onset of the first meiosis, generated tetrads of haploid cells with the morphology of round spermatids and initiated protamine transcription.