Three polypeptides (β, γ and δ) homologous to α-dendrotoxin, an inhibitor of certain voltage-activated K+ channels, were found to elevate the cytosolic free concentration of calcium ([Ca2+]c) in isolated central nerve terminals. Relative to α-dendrotoxin (EC50 − 2.1 nM), the β-, γ- and δ-toxins were 790-, 214- and 5.7-fold less effective; no additivity was apparent in the toxins' effects on [Ca2+]c. Each toxin antagonized the high affinity binding of 125I-labelled α- and δ-dendrotoxin to synaptosomes but with different potencies. The mutual interaction of α- and δ-dendrotoxin with the acceptor appeared complex, the inhibition curves being noticeably extended. For the inhibition of binding of α- and δ-dendrotoxin, the respective Ki's (nM) observed for α, β, γ and δ toxins were 0.78, 50, 99, 8, and 2.3, 95, 61, 0.53. Apparently, interactions of α- and δ-, but not β- or γ-dendrotoxin with the acceptor are closely coupled to an inhibition of K+ channel(s) as observed indirectly by elevation of [Ca2+]c.