Bathing hippocampal slices in the potassium channel blocker tetraethylammonium (TEA), while stimulating the Schafer collaterals at a low frequency, induces Ca²⁺ ‐dependent, N‐methyl‐D‐aspartate (NMDA) receptor‐independent long‐term potentiation of synaptic transmission (LTP_k) in CA1 neurons. We have combined ratio imaging of fura‐2 and mag‐fura‐5 in hippocampal CA1 neurons with intracellular and field recordings to evaluate postsynaptic Ca²⁺ changes that occur in the induction of LTP_k. Test stimuli were applied at 0.05 Hz to stratum radiatum in the presence of the NMDA receptor antagonists D, L‐2‐amino‐5‐phosphonovaleric acid (100μM) or MK‐801 (10μM). During TEA exposure (15–25 mM; 10 min), cells fired prolonged action potentials both spontaneously and in response to test stimuli resulting in transient, micromolar Ca²⁺ accumulations in both somata and dendrites. The initial EPSP slope, measured 60 min after TEA wash‐out, was potentiated to approximately 200% of control. The Ca²⁺ channel blocker nimodipine (10 μM) greatly reduced Ca²⁺ transients in both magnitude and duration and prevented LTP_k induction. Pretreatment of slices with compounds that block metabotropic glutamate receptor (mGluR)‐stimulated phosphoinositide hydrolysis, L‐2‐amino‐3‐phosphonopropionic acid (L‐AP3, 50‐200 μM) or L‐aspartate‐β‐hydroxamate (50–100 μM), as well as protein kinase C (PKC) inhibitors (sphingosine, 20 μM; RO‐31‐8220, 0.2 μM; or calphostin C, 2 μM) also blocked LTP_k. Ca²⁺ transients were unaffected by L‐AP3 or RO‐31‐8220. These findings suggest that Ca²⁺ influx through voltage‐gated channels and co‐activation of PKC by mGluRs are both necessary for induction of LTP_k. Activation of mGluRs must also occur in NMDA receptor‐dependent induction paradigms, but is possibly of lesser importance owing to the much greater gating of Ca²⁺ directly into the dendritic spines. © 1994 Wiley‐Liss, Inc.