We investigated whether previous gubernacular denervation in TS rats changes the gubernacular contractile response to or binding capacity of calcitonin gene-related peptide receptors. In TS rats there is excessive calcitonin gene-related peptide in the genitofemoral nerve and 85% of the male rats have cryptorchidism. TS rats and controls underwent genitofemoral nerve transection or sham operation at day 0. On day 3 gubernacula were cultured with or without calcitonin gene-related peptide to observe contractions. Gubernacular frozen sections were incubated with 125iodine calcitonin gene-related peptide with or without unlabeled calcitonin gene-related peptide. Exposed x-ray films were quantified by computerized densitometry. In the sham operated controls contractility increased from 15 to 55% by adding calcitonin gene-related peptide compared with 5% and 10%, respectively, in the TS rats. After genitofemoral nerve denervation exogenous calcitonin gene-related peptide increased contractility to 90% in controls and 75% in TS rats. Previous genitofemoral nerve transection increased specific 125iodine calcitonin gene-related peptide binding 21% in controls and about 100% in TS rats. Genitofemoral nerve transection in TS rats restored gubernacular contractile response to calcitonin gene-related peptide in vitro and doubled the binding capacity of calcitonin gene-related peptide receptors.