Neuronal Na+ and K+ channels elicit currents in opposing directions and thus have opposing effects on neuronal excitability. Mutations in genes encoding Na+ or K+ channels often interact genetically, leading either to phenotypic suppression or enhancement for genes with opposing or similar effects on excitability respectively. For example, the effects of mutations in Shaker (Sh), which encodes a K+ channel subunit, are suppressed by loss of function mutations in the Na+ channel structural gene para, but enhanced by loss of function mutations in a second K + channel encoded by eag. Here I characterize three novel mutations that suppress the effects of a Sh mutation on behavior and neuronal excitability. Recombination mapping localized the mutations to the eag locus, and I used sequence analysis to determine that two of the mutations are caused by a single amino acid substitution (G297E) in the S2-S3 linker of Eag. Because these novel eag mutations confer opposite phenotypes to eag loss of function mutations, I suggest that eag G297E causes an eag gain of function phenotype. I hypothesize that the G297E substitution may cause premature, prolonged or constitutive opening of the Eag channels by favoring the "unlocked" state of the channel. The third mutation has two amino acid substitutions in Eag (A259V and E762V) and may also be a gain of function allele of eag . Interestingly, these mutations appear to manifest their most obvious phenotypes under conditions that prolong the action potential.