BackgroundTaipans of the genus Oxyuranus are predominately mammal-eating specialists and a majority of Australian brown snakes of the sister genus Pseudonaja are generalist predators, feeding on mammals, lizards and frogs. In this paper, venom composition of several related mammaleating species was compared using shotgun proteomics. ResultsVenom of Oxyuranus temporalis consisted predominately of α-neurotoxins (three-finger toxin family) and was deficient in phospholipase A2 neurotoxins. In contrast, PLA2 neurotoxins (taipoxin and paradoxin) were abundant in the venoms of other mammal-eating taipan species -Oxyuranus scutellatus and O. microlepidotus. Variation in neurotoxic PLA2 expression was also recorded in mammal-eating brown snakes, some species having high venom levels of textilotoxin or related homologues, for example Pseudonaja textilis and P. nuchalis, and others, such as P. ingrami, lacking them. Venom prothrombinase proteins (fX and fV) were expressed in most mammalivorous lineages, being particularly abundant in some Pseudonaja species. Notably, Oxyuranus temporalis venom was deficient in venom prothrombinase despite a mammal-based diet. Expression of an α-neurotoxin that is lethal to rodents (pseudonajatoxin b) was profoundly down-regulated in Pseudonaja textilis venom sample from Queensland and highly up-regulated in the sample from South Australia despite a report that the snake feeds on rodents in both regions. ConclusionRelated species of taipans and brown snakes that feed on small mammals express different sets of venom proteins toxic to this vertebrate group. This suggests an involvement of factors other than prey type selection in shaping venom proteome composition.