Long-term depression (LTD) of field excitatory postsynaptic potentials was induced in the medial path of the dentate gyrus in juvenile rats in vitro by a protocol involving returning the Ca2+ concentration of the external media to the control level (2 mM) following a period (30 min) in low Ca2+ (1.2 mM), with stimulation at the test frequency throughout. Directly increasing Ca2+ from the control level did not induce LTD (or long-term potentiation). Such LTD showed mutual occlusion with low frequency stimulation (LFS, 1 Hz, 900 stimuli)-induced LTD. The Ca2+-induced LTD was shown to be induced by the procedure of elevating the Ca2+ from the low to the control concentration, and not by the procedure of lowering of Ca2+, as full amplitude LFS induced LTD could be induced in the low Ca2+ media. Ca2+-induced LTD was inhibited by Ni2+ (25 mu M) and 2-amino-5-phosphonopentanoate (50 mu M), demonstrating the necessity for activation of T/R-type voltage-gated Ca2+ channels and N-methyl-D-aspartate receptors, respectively, (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.