Phylogenetic relationships among the tribes of Onagraceae were studied using sequences of PgiC, a nuclear gene encoding cytosolic phosphoglucose isomerase. Fragments of 21 genes were examined from plants of 15 species representing 11 of the 17 genera in the family and seven of the eight tribes (the newly proposed Gongylocarpeae was not studied). Maximum likelihood analysis provided a phylogenetic tree with 100% bootstrap support for all but one of the clades that indicate tribal relationships, and corroborated results of recent studies based on chloroplast genes and nuclear ITS sequences. PgiC appears to have a greater rate of divergence than the chloroplast genes and provides much phylogenetically useful data. Two PgiC genes were found in each of the two species sampled in Epilobium; they formed two sister clades, with each species having one gene of each type, showing that the species descended from a single ancestral tetraploid. The two species, E. brachycarpum and E. canum, are not closely related, and previous studies showed that the smallest clade including both contained six of the seven sections of Epilobium. Thus, all species of Epilobium except those in section Epilobium (which was not studied) share a common tetraploid origin, refuting the “Stebbins/Raven” model of the origin of tetraploidy in this genus.