1. Dendrotoxins are small proteins isolated from mamba (Dendroaspis) snake venoms. They block some subtypes of voltage-dependent potassium channels in neurons. 2. Dendrotoxins contain 57-60 amino acid residues crosslinked by three disulfide bridges. They are homologous to Kunitz-type serine protease inhibitors, such as aprotinin, although they have little or no antiprotease activity. 3. Dendrotoxins act mainly on neuronal K+ channels. Studies with cloned K+ channels indicate that alpha-dendrotoxin from green mamba Dendroaspis angusticeps blocks Kv1.1 and Kv1.2 channels in the nanomolar range. In native cells, dendrotoxin appears preferentially to block inactivating forms of K+ current. 4. Dendrotoxins can induce repetitive firing in neurons and facilitate transmitter release. On direct injection to the CNS, dendrotoxins can induce epileptiform activity. 5. Radiolabeled dendrotoxins are useful markers of subtypes of K+ channels in vivo, and structural analogs help to define the molecular recognition properties of different types of K+ channels.