The effect of phenoxybenzamine on in vitro contractile responses of human vasectomy tissues was investigated. Phenoxybenzamine (0.01–10 μmol l ⁻¹ ) produced a differential inhibition of contractions induced by noradrenaline (1–300 μmol l ⁻¹ ) in the human vas deferens in that it blocked the longitudinal but not the circular muscle. Contractions of both muscle types induced by noradrenaline (100 μmol l ⁻¹ ) were inhibited by either prazosin (0.01–10 μmol l ⁻¹ ), a competitive α ₁ -selective adrenoceptor antagonist or benextramine (0.01–10 μmol l ⁻¹ ), an irreversible α ₁ -adrenoceptor blocker, but were unaffected by chloroethylclonidine (0.1–100 μmol l ⁻¹ ), an irreversible α _1B -adrenoceptor blocker. In calcium-free/EGTA (1 mmol l ⁻¹ ) medium, contractions of the longitudinal but not circular muscle induced by noradrenaline (100 μmol l ⁻¹ ) were inhibited by phenoxybenzamine (0.01–1 μmol l ⁻¹ ). Chloroethylclonidine (10–100 μmol l ⁻¹ ) was ineffective on both muscle types in calcium-free medium, but, on readmission of calcium, it markedly inhibited the recovery of longitudinal but not the circular muscle. These results suggest a mechanism for the male contraceptive action of phenoxybenzamine by a selective blockade of longitudinal but not circular muscle contractions. The results are discussed in relation to (i) the possible involvement of receptor reserves for noradrenaline and of α ₁ -adrenoceptor subtypes coupled in the longitudinal and circular muscle to different mechanisms for increasing cytosolic calcium, (ii) a role in the longitudinal muscle for chloroethylclonidine-sensitive α ₁ -adrenoceptors in replenishment of a functional pool of intracellular calcium and (iii) the inhibition of sperm emission by phenoxybenzamine.