Despite the great variability of peptides from the venoms of the marine cone snails known to interact with voltage-gated channels only relatively few have been identified that interact with K⁺ channels. kM-conotoxin RIIIK is a 24 amino acid peptide from Conus radiatus binding to Shaker K⁺ channels expressed in Xenopus oocytes. More recently it was shown that RIIIK specifically blocks mammalien Kv1.2 K⁺ channel with a state dependent affinity of about 200 nM for the closed state of the channel and about 400 nM for the open state at a test potential of 0 mV. In this study the activity of RIIIK on infarct size of a rat heart model for ischemia/reperfusion was assessed. A coronary branch was occluded for 30 min followed by 2.5 hrs of reperfusion. The ischemic area at risk and infarct size were marked with china ink perfusion and triphenyltetrazolium chloride staining, respectively. A bolus i.v. injection of RIIIK administered 5 minutes before reperfusion reduced infarct size from 53 ± 4 % of the risk zone in untreated animals to 30 ± 6 % (n=9). Interestingly the hemodynamic parameters measured where not altered at this dose. These results demonstrate that RIIIK exhibits protective effects for heart cells when administered after an ischemic event.