The mammalian hippocampus, together with subcortical and cortical areas, is responsible for some forms of learning and memory. Proper hippocampal function depends on the highly dynamic nature of its circuitry, including the ability of synapses to change their strength for brief to long periods of time. In this study, I focused on pre- and postsynaptic effects of convergent glutamatergic and cholinergic axons at Schaffer collateral synapses in area CA1 of acute hippocampal slices. Brief trains of synaptic stimulation (30 stimuli at 100 Hz) in stratum radiatum caused a transient depression of evoked excitatory postsynaptic currents (EPSCs) and elicited postsynaptic Ca ²⁺ waves in the dendrites of CA1 pyramidal neurons. Transient depression, lasting 2–3 minutes, resulted from a decrease in presynaptic glutamate release, as synaptic currents through NMDA- and AMPA-type glutamate receptors were depressed similarly, and depression was accompanied by an increase in the paired-pulse ratio for each response type. Transient depression is prevented by blockade of metabotropic glutamate (mGluR) and muscarinic acetylcholine (inAChR) receptors, presumably located presynaptically. These two receptor types—acting together—cause depression. Blockade of a single receptor type necessitates significantly stronger conditioning trains for triggering depression. Addition of an acetylcholinesterase inhibitor enables depression from previously insufficient conditioning trains. Postsynaptic Ca²⁺ waves were also due to synaptic activation of mGluR and mAChR, and could be blocked pharmacologically without preventing transient depression. During the period of depression, the ability of additional synaptic trains to elicit Ca²⁺ waves was diminished, suggesting complex interactions between pre- and postsynaptic effects of G_q-coupled metabotropic receptor activation. Some points of experimental regulation of transient depression and Ca²⁺ waves are described, and the possibility of differential regulation is discussed. The convergent glutamatergic and cholinergic afferent inputs studied here, one intrinsic to the hippocampus and the other likely originating in the medial septum, may regulate CA1 network activity, the induction of long-term synaptic plasticity, and ultimately hippocampal function.