ABSTRACT Two mutants of Drosophila melanogaster, parats 1 (1-53.9) and napts (2-56.2) both display similar temperature-sensitive paralysis associated with blockage in the conduction of nerve action potentials, suggesting that the two gene products have a similar function. This idea is supported by the observation that the double mutant is unconditionally lethal. Genetic analysis of this synergistic interaction has revealed the following: 1) it specifically involves the para and nap loci; (2) all para alleles interact with napts, but the strength of the interaction varies in an allele-dependent fashion; (3) lethality of the double mutant occurs during the first larval instar with parats 1 but differs with other para alleles; (4) hypodosage of para + causes lethality in a napts background. These results together with previous electrophysiological, behavioral and pharmacological studies of these mutants suggest that both para and nap affect sodium channels and possibly encode different subunits.