This study examined, in adult monkeys, the role that gonadotropin independent mechanisms play in compensation of testosterone (T) secretion by the testis that remains following unilateral orchidectomy (UO). We employed a model ("testicular clamp"), in which endogenous gonadotropin secretion was abolished with a GnRH receptor antagonist, and the gonadotropin drive to the testes was concomitantly replaced with an invariant intravenous pulsatile infusion of recombinant human LH and FSH (1 min pulse every 2.5 h: LH, 0.08-0.12 IU/kg/pulse; FSH, 0.12-0.32 IU/kg/pulse) that provided the Leydig cells with a physiological stimulus. Within 5 h of UO (n = 5), circulating T concentrations had declined to 43% of pre-UO levels. By day 4, however, loss of the first testis was partially compensated, as reflected by the finding that circulating T had reached a plateau of 67% of the pre-UO level, where it remained for the duration of the study (39 days). That the recovery in circulating T was the result of increased T secretion by the remaining testis was suggested by the finding that the pulsatile pattern and decay of T during the inter-gonadotropin pulse interval before and after UO was indistinguishable. Interestingly, inhibin B production by the remaining testis also showed a delayed, albeit, minor compensation (13% on day 10-11; P > 0.05) after loss of the first testis. These results suggest that compensation in T production by the remaining testis following UO in adult monkeys may be achieved, in part, by a gonadotropin independent mechanism that probably involves direct neural inputs to the primate testis.