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Paired shocks revealed a long-lasting suppression of calcium influx with \u223c40% suppression at 400-ms interstimulus intervals and a recovery time constant of \u223c450 ms. Blocking activation of postsynaptic olfactory bulb neurons with APV\/CNQX reduced this suppression. The GABA<jats:sub>B<\/jats:sub>receptor agonist baclofen inhibited calcium influx, whereas GABA<jats:sub>B<\/jats:sub>antagonists reduced paired-pulse suppression without affecting the response to the conditioning pulse. We also imaged transmitter release directly using a mouse line that expresses synaptopHluorin selectively in ORNs. We found that the relationship between calcium influx and transmitter release was superlinear and that paired-pulse suppression of transmitter release was reduced, but not eliminated, by APV\/CNQX and GABA<jats:sub>B<\/jats:sub>antagonists. These results demonstrate that primary olfactory input to the CNS can be presynaptically regulated by GABAergic interneurons and show that one major intracellular pathway for this regulation is via the suppression of calcium influx through N-type calcium channels in the presynaptic terminal. 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