We investigated the role of peritubular cell-Sertoli cell interactions in the control of Sertoli cell function by androgens. Decreased FSH-inducible aromatase activity and increased secretion of androgen-binding protein (ABP) were used as parameters of androgen action on Sertoli cells. It is demonstrated that coculturing Sertoli cells with limited amounts of peritubular cells (20%) has only marginal effects on inducible aromatase activity or ABP secretion, but markedly increases the response of these parameters to androgens. Conditioned media derived from peritubular cells pretreated with androgens mimick the effects observed in the coculture system. Evidence is presented that androgen action on peritubular cells is mediated by an androgen receptor and that the concentration of this receptor is increased up to 3-fold by androgens. Preliminary experiments suggest some analogy between the peritubular cell factors that stimulate ABP production and those that inhibit aromatase induction. The active principles responsible for both activities are thermolabile trypsine-sensitive proteins with a mol wt between 50,000-100,000, and androgen induction by both activities shows an identical time course, characterized by a 4-day latent period. Nonetheless, much higher concentrations of peritubular cell secretion products seem to be required to inhibit aromatase induction than to stimulate ABP production, indicating that the active principles are not necessarily identical. It is concluded that peritubular cell secretion products mimick and mediate not only stimulatory but also inhibitory effects of androgens on Sertoli cells.