The selective 5-HT2 receptor blocker ketanserin was found to reduce maximal urethral pressures in healthy females by about 40% without reducing blood pressure. In vitro, ketanserin completely or almost completely reduced contractions of the isolated female rabbit urethra induced by phenylephrine, noradrenaline (NA) and electrical field stimulation. The drug was less effective against responses evoked by clonidine and 5-hydroxytryptamine (5-HT). 5-HT-induced contractions were effectively reduced by methysergide, but little affected by prazosin and rauwolscine. In concentrations exceeding 10(-7) M ketanserin significantly increased efflux of 3H in 3H-NA preloaded preparations of rabbit urethral muscle. Low concentrations of 5-HT, less than 10(-6) M, had slight inhibitory effects of 3H release, whereas 5-HT 10(-5) M caused a significant increase. It is concluded that ketanserin counteracts the effects of postjunctional alpha 1-adrenoceptor stimulation in isolated rabbit urethra. Such an effect might also explain its urethral pressure lowering action in man.