It has been suggested that the stimulation of the secretion of PRL by the alpha 2 adrenergic receptor antagonists (yohimbine, piperoxane) results from blockade of an inhibitory influence imposed on PRL release by the central alpha 2 receptors (7, 15). Our present results do not support these conclusions for the following reasons: 1) The effectiveness of the alpha 2 receptor antagonists yohimbine (YOH), rauwolscine (RAU), Wy 26392 and idazoxan (IDAZ) respectively to activate secretion of PRL was not related to their alpha 2 antagonist potencies. RAU was more effective in activation of PRL secretion than either YOH or Wy 26392 although it had a similar alpha 2 antagonist activity, while IDAZ, the most potent alpha 2 blocker among the four compounds, did not stimulate PRL secretion. 2) The PRL-releasing effect of YOH or Wy 26392 was reversed by the alpha 2 agonist clonidine but the same effect of RAU was not, speaking against a common alpha 2-mediated mechanism of action of the three antagonists. 3) The PRL-stimulating effect of YOH, RAU or Wy 26392 persisted following inhibition of NE synthesis and presumably release with FLA 63, DDC or combination of reserpine and DDC. 4) Conversely, we found no indication for an inhibiting influence of activation of the alpha 2 receptors on the secretion of PRL. We conclude that the stimulation of PRL secretion by the alpha 2 receptor antagonists is not derived from blockade of the central alpha 2 receptors but from other, not yet defined properties of the drugs.