Despite the dramatic development of sexually transmissible diseases, the antiviral capabilities of testicular cells have not yet been explored. Interferons (IFNs) are proteins playing a key role in the antiviral defense system, their activity being mediated by several IFN-induced proteins. In the present study, we have investigated both the expression of IFN and of the three main IFN-induced proteins by isolated testicular cells. The highest responders to a viral stimulation in terms of IFN production are the Leydig and the Sertoli cells, followed by peritubular cells and testicular macrophages, while germ cells are devoid or virtually devoid of IFN and IFN-induced protein expression. Sertoli cells constitutively expressed the three IFN-induced proteins tested, and their levels were greatly increased after exposure to Sendai virus. Peritubular cells were also able to markedly express these three proteins after viral exposure. In conclusion, we hypothesize that, for a virus coming from the blood, the first testicular line of defence is ensured by Leydig cells and testicular macrophages, the second line being ensured by the myoid cells, lining the seminiferous tubules, and by Sertoli cells. These two barriers are probably fundamental in protecting both androgen production and spermatogenesis.