By focusing exclusively on the highly conserved inverted repeat region of the chloroplast genome, we extend comparative restriction site mapping to greater evolutionary depths than those to which it has been applied previously. A cladistic analysis of inverted repeat restriction site data is presented in order to enhance understanding of relationships within the Asteridae and to test the possible monophyly of the Asteridae. A total of 114 species, representing 33 families of Asteridae and eight families of Rosidae and Dilleniidae (sensu Cronquist) was examined, of which 99 species exhibited restriction maps of sufficient colinearity to be included in the phylogenetic analysis. Analysis with four restriction endonucleases identified a total of 77 restriction sites, 55 of which were phylogenetically informative. Parsimony analysis identified six major groups that broadly correspond to traditionally recognized orders in the Asteridae: Asterales, Boraginales, Dipsacales, Gentianales, Scrophulariales plus Lamiales, and Solanales. The results further suggest that the Asteridae, as traditionally circumscribed, are not monophyletic. The Apiaceae, Araliaceae, Cornaceae, Hydrangeaceae, Loasaceae, and possibly the Fouquieriaceae, all placed previously by Cronquist in subclasses Dilleniidae and Rosidae, should be included in a broadly defined Asteridae. The Cornaceae, Hydrangeaceae and Loasaceae appear closely related. Unexpected results include a probable sister-group relationship between the Apiales and Dipsacales, and the placement of the Menyanthaceae in the Asterales. Familial relationships within several orders and interordinal relationships remain poorly resolved.