Modafinil did not affect spontaneous and K+-evoked [H-3]5-HT efflux from cortical synaptosomes while it increased K+-evoked tritium efflux from cortical slices, an action that became stronger in the presence of paroxetine. In contrast, DL-fenfluramine and fluoxetine were able to enhance spontaneous and/or K+-evoked tritium efflux from synaptosomes and slices. These results suggest that modafinil does not affect 5-HT transmission from cortical synaptosomes and that its 5-HT releasing action is different from that of DL-fenfluramine and fluoxetine. (C) 2001 Elsevier Science B.V. All rights reserved.