Studies in recent years have clearly established that, in addition to the well known endocrine regulation by gonadotrophin hormones, spermatogenesis is under the modulatory control of a complex set of paracrine regulators. Whereas the role of Leydig cells (testosterone) and of Sertoli cells (nurce cells of germ cells) in spermatogenesis has focused most of the attention, until recently little was known about the contribution of germ cells in the spermatogenetic process. This was the aim of the present experiments. We have used, in vitro, 3 complementary approaches; 1) we measured the influence of the removal of germ cells contaminating Sertoli cell cultures by a hypotonic treatment; 2) in coculture, we examined to what extend isolated germ cells could affect Sertoli cell function; 3) we investigated the effects of germ cell conditioned media on Sertoli cell cultures. Our results indicate that germ cells are able to modulate Sertoli cell function in vitro. This germ cell influence varies according to: 1) the germ cell fraction tested (pachytene spermatocytes, early spermatids or cytoplast from elongated spermatids/residual bodies); 2) the parameter of Sertoli cell function studied (inhibition of oestradiol; stimulation of androgen-binding protein, transferrin...); 3) the age of the Sertoli cell donors; 4) the hormonal environment (+/- FSH). Furthermore we wave demonstrated that germ cell effects were partly at least mediated via proteinaceous factor(s) detected in germ cell spent media. Taking into account previous in vivo studies and these in vitro results, we have hypothesized that germ cells, in conjunction with hormones (LH, FSH, testosterone) play an important role in the ontogenesis of Sertoli cells and therefore in spermatogenesis.