Recent studies have shown that the two main types of cortical neurons, pyramidal and nonpyramidal, have different origins and use different migratory routes--radial and tangential respectively. The role of neurotransmitters in radial migration is well known; however, there are no data about their effect on intracellular calcium--[Ca(2+)](i)--in tangentially migrating cells. We have performed ratiometric and confocal calcium imaging of 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine labelled tangentially migrating neurons in the intermediate zone cells of fetal rat coronal slices. Superfusion with N-methyl-D-aspartic acid (NMDA) leads to an increase in [Ca(2+)](i), which is blocked by the antagonist APV or the presence of Mg(2+) in the medium. Kainate produced an increase in [Ca(2+)](i) that could be blocked by the non-NMDA antagonist CNQX. Muscimol, an agonist of GABAa-receptors, produced a transitory increase in [Ca(2+)](i) that was blocked by the specific antagonist bicuculline or the presence of tetrodotoxin in the medium. We conclude that tangentially migrating cells display consistent [Ca(2+)](i) changes in response to agonists of NMDA, non-NMDA and GABAa receptors, suggesting that these cells are quite mature and homogeneous. The endogenous activation of these receptors may have either a direct effect on tangential migration or modulate the response of migrating cells to external cues.