A group of men treated with testicular irradiation for carcinoma in situ in the remaining testis after orchidectomy for unilateral testicular germ cell cancer was used as a model to study of the effect of selective eradication of germ cells on the levels of serum inhibin B in the human male. Thirteen men with verified spermatogenesis and detectable preirradiation levels of serum inhibin B (median, 55; range, 23-193 pg/mL) were investigated before and after testicular irradiation (14-20 Gy). All patients had undetectable levels of inhibin B 2-12 months (median, 5 months) after radiotherapy (<20 pg/mL). Correspondingly, serum FSH increased in all men after radiotherapy [from a median of 9.6 (range, 3.0-24) IU/L to a median of 28 (range, 15-70) IU/L); P < 0.001]. Histological investigation showed a Sertoli cell-only pattern in all patients after radiotherapy. Neither LH nor testosterone showed a significant decrease after radiotherapy. Our data indicate that inhibin B production sufficient to maintain detectable serum levels in adults requires spermatogenic activity.