Omega conotoxins are peptides from snail venom. Two variants, omega CgTX and omega CmTX derived from two species of Conus, are the subjects of this report. Part I of this report reviews and discusses the ability of these toxins to inhibit Ca channels and synapses in different tissues from various species of animals. The potencies of these toxins vary depending on the target tissue, consonant with the notion that synaptic Ca channels have changed in the course of evolution. Part II introduces the notion that in contrast to inorganic Ca channel blockers, which act by reducing the amount of Ca2+ ions that can permeate an open channel, omega toxins act by reducing the availability of functional Ca channels. Thus, Ca channel-inhibition by omega toxins and that by inorganic blockers are expected to produce qualitatively different alterations in the distribution of intracellular Ca2+. Consistent with this expectation, the dose-response curves of inorganic blockers and omega CmTX differ. The dose-response curves of inorganic blockers are thought to reflect the cooperativity of Ca2+ ions in mediating transmitter release. In contrast, comparison of experimental and theoretical dose-response curves of omega CmTX leads us to propose the hypothesis that Ca channels normally do not act cooperatively to effect transmitter release.