A wide range of prazosin pA2/pKB values have been reported in rat vas deferens: varying between 8.32 and 9.35, and the receptors present have been identified as α1A‐, α1D‐ in addition to α1A‐, or α1L‐adrenoceptors (see 1). Studies differ in choice of NET blocker: cocaine or desipramine (DES). We have now investigated the effects of NET blockers on the potency of prazosin at antagonizing contractions to norepinephrine (NE) in epididymal portions of rat vas deferens.Cocaine significantly increased NE potency by revealing the α1D‐adrenoceptor‐mediated component. However, in the presence of cocaine (10 µM), DES (0.1‐10 µM) produced concentration‐dependent inhibition of the response to NE. Prazosin pKB values against NE varied from 8.32 (control), and 8.50 (DES 0.1µM), to 9.05 (cocaine 3 µM), with the lower values indicative of α1A‐adrenoceptor potency, and the higher value indicative of α1D‐adrenoceptor potency. Cocaine and DES (both 0.3 μM) potentiated the contractile response to nerve stimulation, but higher concentrations of DES inhibited the response.Prazosin potency against NE was increased in the presence of NET blockade by cocaine. However, DES does not increase the potency of prazosin as it acts as an α1‐adrenoceptor antagonist over the concentration range that it blocks NET. DES may not be a suitable NET blocker for use in α1‐adrenoceptor studies.(1) Docherty JR (2013). J Auton Autacoid Pharmacol 33, 49‐57.