Within the male gonad, TNF alpha is secreted by macrophages in the interstitial tissu and by germ cells in seminiferous tubules. TNF alpha receptors (type I) have been detected in the somatic cells of the testis (i.e. Leydig and Sertoli cells). TNF alpha has two type of action within the testis: the cytokine has an anti-hormonal role and play a role in the interactions between Sertoli and germ cells. Anti-hormonal actions of TNF alpha are (i) inhibition of LH-induced testosterone production in Leydig cells and (ii) inhibition of FSH-induced inhibin production in Sertoli cells. Moreover, TNF alpha; produced by germ cells, enhanced expression of growth factors in Sertoli cells (IGFBP3, receptor type I of bFGF) and enhanced production of energetic metabolite important for germ cells such as lactate (via enhancement of lactate dehydrogenase enzyme, isoform 5). Moreover, Fas/Fas ligand system, proteins related to TNF alpha, seem to play a key role in the protection of germ cells against the immune system within the testis. In conclusion, TNF alpha and related proteins, could play a great role in testicular functions such as spermatogenesis (interactions between Sertoli and germ cells) and in the interactions between immune system and spermatogenesis (role of TNF alpha originating form blood/testicular macrophages, role of Fas/Fas ligand system).