The effects of (+)- and (-)-amosulalol on the spontaneous and nerve stimulation-evoked outflow of radioactivity following loading of the rat right ventricle with [3H]noradrenaline and on the contractions evoked either by nerve stimulation or by isoprenaline are reported. The spontaneous outflow of radioactivity was increased by (+)- and (-)-amosulalol at 10(-5) M by a cocaine- and idazoxan-insensitive mechanism. (+)-Amosulalol at 10(-5) M and (-)-amosulalol at 10(-6)-10(-5) M increased the nerve-evoked outflow of radioactivity. The ability of (+)-amosulalol to increase outflow was reduced by cocaine and idazoxan, whereas the ability of (-)-amosulalol to increase outflow was unaltered by cocaine but abolished by idazoxan pretreatment. This suggests that (-)-amosulalol but not (+)-amosulalol, at 10(-6) M is an alpha 2-adrenoceptor antagonist and that (+)- but not (-)-amosulalol, at 10(-5) M, inhibits the neuronal uptake process for noradrenaline. (-)-Amosulalol was a more potent inhibitor of the contractile responses evoked by nerve stimulation than (+)-amosulalol. The contractile responses of the electrically driven direct muscle stimulated right ventricle to isoprenaline were inhibited by (+)-amosulalol at 10(-6) M and (-)-amosulalol at 3 X 10(-8)-10(-6) M. (-)-Amosulalol (pA2 = 7.9) was 100 times more potent than (+)-amosulalol (pA2 = 5.9) as a beta 1-adrenoceptor antagonist. In addition, the maximal responses to isoprenaline were reduced by the higher concentrations of (-)-amosulalol tested (10(-7)-10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)