omega-Conopeptides are antagonists of subtypes of neuronal calcium channels. Two omega-conopeptides, SVIB and MVIIC, have recently been identified which have a novel specificity for these ionophores. The authors have tested the actions these peptides, as well as the more selective MVIIA, on the release of glutamic acid and gamma-aminobutyric acid (GABA) in the hippocampus in vivo. For the assay of peptide effects on release, the authors used microdialysis to deliver multiple pulses of elevated potassium to the brain extracellular fluid. Peptide effects were quantitated from the decrement of the release with peptide perfused through the probes, in comparison to that in control experiments. Synthetic MVIIC caused a 40-50% decrement in the release of both glutamate and GABA at a probe concentration of about 200 nM. Synthetic SVI-B caused a 50% block at about 20-40 microM, while about 200 microM of MVIIA was required for 50% block. Chromatographic experiments showed that differences in potency between MVIIC and MVIIA were not explained by differential degradation. Blockade of release was also observed in the thalamus. MVIIC provides a tool for investigating the role of calcium mediated release of glutamate and GABA in physiological and pathological processes in the mammalian brain in vivo.