Despite the great variability of the conus peptides characterized until now only relatively few have been identified that interact with K+ channels. κM-conotoxin RIIIK (κM-RIIIK) is a 24 amino acid peptide from Conus radiatus, which is structurally similar to μ-conotoxin GIIIA, a peptide known to block specifically skeletal muscle Na+ channels. Recently, it has been shown that κM-RIIIK does not interact with Na+ channels, but inhibits Shaker potassium channels expressed in Xenopus oocytes. It was demonstrated that κM-RIIIK binds to the pore region of Shaker channels and a teleost homologue of the Shaker channel TSha1 was identified as a high affinity target of the toxin. In contrast the mammalian Shaker-homologues Kv1.1, Kv1.3, Kv1.4 are not affected by the toxin. In this study the activity of κM-RIIIK on other mammalian Kv1 K+ channels expressed in Xenopus oocytes was investigated. We demonstrate that κM-conotoxin RIIIK up to 5 μM exhibits no significant effect on Kv1.5 and Kv1.6 mediated currents, but the human Kv1.2 K+ channel is blocked by this peptide. The binding of κM-RIIIK to Kv1.2 channels is state dependent with an IC50 for the closed state of about 200 nM and for the open state of about 400 nM at a test potential of 0 mV. κM-conotoxin RIIIK is the first conotoxin described to block human Kv1.2 potassium channels.