We have previously demonstrated that systemic administration of testosterone propionate (TP) to adult hamsters accelerates the rate of facial nerve regeneration following crush axotomy of the facial nerve at its exit from the stylomastoid foramen. In this study, we utilized flutamide, a potent nonsteroidal antiandrogen, in conjunction with radioisotopic labeling procedures for the assessment of facial nerve regeneration rates to test the hypothesis that TP exerts its accelerative effects on facial nerve regeneration through a receptor-mediated mechanism. Castrated adult male hamsters were subjected to right facial nerve crush axotomies and divided into three groups of axotomized animals: castrate plus one subcutaneous TP implant plus daily injections of flutamide, castrate plus one subcutaneous TP implant plus vehicle injections, and castrate only plus sham implant and vehicle injections. There were two postoperative timepoints: 4 and 7 days. In agreement with previous studies, systemic administration of TP resulted in an approximately 26% increase in the rate of regeneration of the fastest growing population of axons. Exposure to flutamide completely abolished the TP-induced accelerative effects on facial nerve regeneration rate. As a bioassay for the effectiveness of systemic administration of flutamide by subcutaneous injection, seminal vesicle weights were collected from all groups at the end of the postoperative time and compared as a percentage of the seminal vesicle weights of intact (nongonadectomized) male control animals. Castration greatly reduced seminal vesicle weights, whereas exogenous TP restored the seminal vesicle weights to those of the intact male. Flutamide blocked the effects of exogenous TP on seminal vesicle weights and reduced them to castrate levels.(ABSTRACT TRUNCATED AT 250 WORDS)