The buzzatii complex of the mulleri subgroup (Drosophila repleta group) consists of three clusters of species whose evolutionary relationships are poorly known. We analyzed 2,085 coding nucleotides from the xanthine dehydrogenase (XDH:) gene in the 10 available species of the complex and Drosophila mulleri and Drosophila hydei. We adopted a statistical model-fitting approach within the maximum-likelihood (ML) framework of phylogenetic inference. We first modeled the process of nucleotide substitution using a tree topology which was reasonably accurate. Then we used the most satisfactory description so attained to reconstruct the evolutionary relationships in the buzzatii complex. We found that a minimally realistic description of the substitution process of XDH: should allow six substitution types and different substitution rates for codon positions. Using this description we obtained a strongly supported, fully resolved tree which is congruent with the already-known (yet few) relationships. We also analyzed published data from three mitochondrial cytochrome oxidases (CO I, II, and III). In our analyses, these relatively short DNA sequences failed to discriminate statistically among alternative phylogenies. When the data of these three gene regions are combined with the XDH: sequences, the phylogenetic signal emerging from XDH: becomes reinforced. All four of the gene regions evolve faster in the buzzatii and martensis clusters than in the stalkeri cluster, paralleling the amount of chromosomal evolution.