Dopamine has been implicated in various brain functions and the pathology of neurological diseases. In the hippocampus, dopamine has been shown to induce acute depression of synaptic transmission in the CA1 region, but it remains largely unknown how it works in the CA3 region. We here report that dopamine induces acute synaptic potentiation at the synapse formed by mossy fibers (MFs) on mouse hippocampal CA3 pyramidal cells, but not at converging associational/commissural synapses. Dopamine potentiated both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) components of MF synaptic responses similarly in respect of the magnitude and time course. The dopamine-induced potentiation was intact in the presence of picrotoxin, required activation of D1-like receptors and was apparently occluded by an activator of adenylate cyclase. The potentiation was accompanied by a decrease in magnitude of synaptic facilitation, suggesting the presynaptic site for the expression of the potentiation. The present study is the first demonstration of acute potentiation of hippocampal excitatory synaptic transmission by dopamine, which is most probably mediated by presynaptic D1-like receptor–cAMP cascades.