We tested the ability of L-AP4 to modulate high voltage-activated (HVA) calcium (Ca2+) currents in pyramidal neurones acutely isolated from the adult rat (4–8 weeks). Whole cell recordings, with barium (Ba2+) ions as the charge carrier, were performed. L-AP4 reduced HVA Ca2+conductances in 86% of the recorded cells. Saturating concentrations of L-AP4 inhibited about 21% of the current (± 8.3%,n= 8), although great variability was observed. Interestingly, low micromolar concentrations of (1S,3R)-1-aminocyclo-pentane-1,3-di-carboxylic acid (1S,3R-ACPD) and (2S,3S,4R)-α-(carboxy-cyclopropyl)-glycine (1-CCGI) had weaker effects than L-AP4. MAP4 fully antagonized the L-AP4-mediated reduction of HVA Ca2+currents. These findings suggest the involvement of the AP4-sensitive receptor in the control of both cellular excitability and transmitter release in rat neocortical neurones.