Recombinational dissection of theShrK0120strain ofDrosophila melanogasterdemonstrated that its extremely prolonged neuromuscular transmission, a defect qualitatively different from otherShalleles, results from a synergistic interaction with a second site mutation. This new mutation caused spontaneous repetitive firing in motor axons and increased transmitter release. Complementation tests showed that it is allelic toeag.Combining eithereagallele with variousShalleles reproduced the same extreme defect observed in the originalShrK0120strain. Thus, from their effects on neuromuscular transmission no qualitative difference amongShalleles is apparent whileSh, eag, andeag Shdouble mutant individuals can be uniquely distinguished. Pharmacological experiments indicated thatShaffects a membrane component sensitive to the potassium channel blockers 4-AP and TEA whileeagaffects a component sensitive to TEA but not 4-AP. We suggest thateagandShpreferentially disrupt different potassium currents explaining their synergistic interaction.