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The Central American Loxocemus and the pythons are assigned to sister subfamilies Loxoceminae and Pythoninae, within the weakly characterized family Boidae. They share the character of the left cerebral artery foramen being larger than the right. Within the Henophidia, paired subcaudal scales associate these subfamilies with Xenopeltis and the Uropeltidae.

Twenty-nine discrete variables were coded as 52 binary characters. Nine continuous (meristic) variables were examined. A method is described by which 18 binary characters were selected from seven of these variables, for inclusion in the data set. With Loxocemus and Xenopeltis as outgroups, the data were analysed by a compatibility method. The Pythoninae are resolved into tribes Pythonini and Moreliini on the basis of complementary synapomorphies. The Pythonini have only the genus Python, for the African and Asiatic species, including reticulatus and timoriensis. The Moreliini have all of the Australasian species, in two genera: Aspidites and Morelia.

A phylogenetic analysis of the two tribes is presented, with incomplete resolution of the Moreliini. The two tribes overlap in the areas of the Moluccas and Timor. It is postulated that: Loxocemus plus Pythoninae represent a Laurasian stock; south-east Asia was the primary centre of radiation of the Pythoninae; by the Miocene dispersal to Australasia had occurred, where there was a second radiation.