This paper presents the first molecular phylogenetic analysis of the phylum Ctenophora, by use of 18S ribosomal RNA sequences from most of the major taxa. The ctenophores form a distinct monophyletic group that, based on this gene phylogeny, is most closely related to the cnidarians. Our results suggest that the ancestral ctenophore was tentaculate and cydippid-like and that the presently recognized order Cydippida forms a polyphyletic group. The other ctenophore orders that we studied (Lobata, Beroida, and Platyctenida) are secondarily derived from cydippid-like ancestors, a conclusion that is also supported by developmental and morphological data. The very short evolutionary distances between characterized ctenophore 18S rRNA gene sequences suggests that extant ctenophores are derived from a recent common ancestor. This has important consequences for future studies and for an understanding of the evolution of the metazoans.