(-)-Pindolol (4 mg/kg, i.p.) stereospecifically and selectively inhibited rat brain 5-HT synthesis. The DA and NA synthesis remained unaffected by pindolol (either enantiomer) treatment, and the (-)-pindolol-induced decrease in 5-HT synthesis was not prevented by reserpine pretreatment. The results indicate that, in addition to its beta-adrenergic properties, (-)-pindolol may act as an agonist at synthesis-controlling 5-HT receptors (autoreceptors ?) in the rat CNS.