We have cloned a Kv2 potassium channel from squid optic lobe termed sqKv2. Multiple overlapping sqKv2 cDNA clones differed from one another at specific positions by purine transitions. To test whether the purine transitions were generated by RNA editing, we compared a 360 nucleotide genomic sequence with corresponding cDNA sequences (encoding S4-S6) isolated from individual animals and lying on a single gene and exon. cDNA sequences differed from genomic sequence at 17 positions, resulting in 28 unique sequences. There was invariantly an adenosine in the genomic sequence and a guanosine in the edited cDNA sequences. Two of the edits altered the rates of channel closure and slow inactivation. These results extend selective RNA editing to invertebrate taxa and represents a novel mechanism for the posttranscriptional modulation of voltage-gated ion channels.