The relationship among calcitonin gene-related peptide (CGRP), a neurotransmitter in the genitofemoral nerve, androgens and gubernacular development was studied using rats treated prenatally with the antiandrogen flutamide and the mutant cryptorchid TS rat. We compared these 2 groups with the testicular feminization mouse with androgen insensitivity. Gubernacula from male TS rats and flutamide-treated rats were maintained in organ culture and examined for contractile response to CGRP. Controls were gubernacula from normal rats and vehicle-treated rats, respectively. TS rat gubernacula have an inhibited contractile response to CGRP, whereas flutamide-treated rat gubernacula have an exaggerated response. A similar exaggerated response to CGRP has previously been demonstrated in testicular feminization mouse gubernacula. These results revealed abnormalities in gubernacular contractile response to CGRP in these cryptorchid animal models, implying that CGRP and gubernacular contractility may have key roles in mediating normal inguinoscrotal testicular descent.