The interaction of naftopidil with adrenoceptors was studied in comparison to standard drugs. Naftopidil binds specifically to α1-adrenoceptors. The Ki values are 58.3 nM for naftopidil, 0.43 nM for prazosin, and 197 nM for urapidil. The affinities of naftopidil to α2- and β-adrenoceptor sites are very low (>6,000 and >2,500 nM). Naftopidil relaxes aortic strips precontracted with norepinephrine concentration-dependently, and it shifts the concentration–response curve of norepinephrine in a parallel manner to the right. The pA2 values are 7.10 for naftopidil, 8.85 for prazosin, and 6.25 for urapidil. In pithed rats, naftopidil shifted the dose–response curve of methoxamine at equipotent hypotensive doses to the same extent to the right as does prazosin, but both drugs barely affected (in contrast to phentolamine) the response to norepinephrine. In concentrations that are about 10 times higher than those required for α1-adrenoceptor blockade, naftopidil relaxes (in contrast to prazosin) aortic strips depolarized with K+, and it shifts Ca2+ concentration–response curves to the right (pA2 value of 5.90), thus suggesting Ca2+-channel-blocking activity. Both α-adrenoceptor and Ca2+-blocking activities are exerted to nearly the same extent by both stereoisomers. Naftipidil does not affect the response to isoprenaline-induced effects, indicating that the compound does not possess β-blocking properties.