The relationship between changes in Sertoli cell number and function and changes in circulating inhibin B concentrations was investigated following unilateral orchidectomy (UO) in the adult rhesus monkey. As expected, the 50% loss in Sertoli cells resulting from UO on day 0 was associated with a rapid and corresponding decline in plasma concentrations of inhibin B. The decrease in inhibin B levels was sustained until the remaining testis was removed on day 44, at which time a compensatory 50% increase (P < 0.05) in the number of round spermatids was evident in the absence of a change in Sertoli cell number. Moreover, Sertoli cell number and inhibin B levels among individual monkeys were highly correlated (r2 = 0.65, P < 0.002). Round spermatid number and inhibin B, however, were poorly correlated (r2 = 0.37, P < 0.04). These findings indicate that, in a physiological setting where the negative feedback control system governing the adult primate testis is operational, Sertoli cell number, rather than function, is the primary determinant of circulating inhibin B levels.