The Papuan taipan (Oxyuranus scutellatus canni) is widely distributed throughout much of Papua New Guinea. Although neurotoxicity is a major symptom of envenomation, no neurotoxins have been isolated from this venom. Using a series of size exclusion chromatography steps, we report the isolation of cannitoxin, a presynaptic neurotoxin (44,848 Da) that represents approximately 16% of the whole venom. The toxin displayed high phospholipase A 2 (PLA 2 ) activity (330 Ϯ 5 mol/ min/mg) and caused concentration-dependent (11-66 nM) inhibition of indirect (0.2 ms; 0.1 Hz; supramaximal V) twitches of the chick biventer cervicis nerve-muscle preparation without effecting nicotinic receptor agonists. Prior addition of CSL Taipan antivenom (5 U/ml) or inhibition of phospholipase A 2 activity by incubation with 4-bromophenacyl bromide prevented the inhibition of twitches. Cannitoxin is composed of three different subunits, ␣, , and ␥, with the possibility of two  isomers. However, only the ␣ subunit displayed in vitro neurotoxic activity of its own. Thus, cannitoxin is similar in structure and pharmacology to taipoxin, which has been isolated from the closely related Australian species O. scutellatus scutellatus (coastal taipan).Three species of taipans (genus Oxyuranus) have been identified and are considered to be the world's most venomous snakes (Sutherland and Tibballs, 2001 (Broad et al., 1979). However, t 90 (i.e., time to produce 90% inhibition of indirect twitches) data obtained in the chick biventer cervicis nerve-muscle (CBCNM) preparation indicated that O. scutellatus scutellatus venom is more neurotoxic than that of O. scutellatus canni venom (Crachi et al., 1999b). They also showed that CSL Taipan antivenom (CTPV) was markedly more effective in neutralizing the neurotoxic effects of the Papuan or coastal taipan venoms than that of the inland taipan (Crachi et al., 1999b).Presynaptic neurotoxins act at the motor nerve terminal to either facilitate (e.g., dendrotoxin) or inhibit (e.g., -bungarotoxin, taipoxin, and paradoxin) the release of neurotransmitter. All of the presynaptic inhibitors have phospholipase A 2 (PLA 2 ) activity (Harris, 1991). Taipoxin and paradoxin were isolated from the venoms of O. scutellatus scutellatus (Fohlman et al., 1976) and O. microlepidotus, respectively. Taipoxin is a ternary complex of three subunits, ␣-, -, and ␥-taipoxin, that exists in a stoichiometry of 1:1:1 held together by noncovalent interactions. The ␣ subunit is the only subunit with toxic activity on its own. The  subunit is neutral and exists in two isoforms (i.e.,  1 and  2 ), which are interchangeable in the complex. The ␥ subunit is the largest of the three subunits, and it seems to be glycosylated (FohlArticle, publication date, and citation information can be found at