Several hybrid rescue mutations-alleles that restore the viability of normally lethal hybrids-have been discovered in Drosophila melanogaster and its relatives. Here we analyze one of these genes, Hybrid male rescue (Hmr), asking two questions about its role in hybrid inviability. (1) Does the wild-type allele from D. melanogaster (Hmr(mel)) cause hybrid embryonic inviability? (2) Does Hmr(mel) cause hybrid larval inviability? Our results show that the wild-type product of Hmr is neither necessary nor sufficient for hybrid embryonic inviability. Hmr(mel) does, however, appear to lower the viability of hybrid larvae. The data further suggest (though do not prove) that Hmr(mel) acts as a gain-of-function poison in hybrids. These findings support previous claims that hybrid embryonic and larval lethalities are genetically distinct and suggest that Hmr(mel) is at least one of the proximate causes of hybrid larval inviability.