The influence of (+)- and (-)-oxaprotiline (OXA) given repeatedly on the behavioural effects mediated by alpha 1- and alpha 2-adrenoceptors as well as on the binding to brain alpha 1-adrenoceptors was studied. (+)-OXA given repeatedly for 14 days (but not 3 or 7 days) enhanced exploratory hyperactivity of rats induced by methoxamine injected intracerebroventricularly; (-)-OXA given for 3, but not 7 or 14 days, increased the methoxamine-induced exploration in rats. The locomotor hyperactivity induced in mice by d,1-threo-3,4-dihydroxyphenylserine was increased by repeated (14 days) (-)-OXA but not (+)-OXA. Neither OXA enantiomers given repeatedly modified the clonidine-induced locomotor hypoactivity in mice. Both enantiomers given repeatedly did not change the binding of [3H] prazosin to alpha 1-adrenoceptors (Bmax, KD) in the thalamus and hippocampus. Repeated (+)-OXA increased the affinity of alpha 1-adrenoceptors for phenylephrine in the cortex, thalamus and hippocampus. A similar effect of (-)-OXA was observed in the hippocampus only. The results indicate that both OXA enantiomers are able to enhance the responsiveness of brain alpha 1-adrenergic system, probably via the increase in the affinity of alpha 1-adrenoceptors for their agonists.