Cecropins are insect antibacterial peptides that are part of the insect humoral immune response and could, therefore, be potential targets of natural selection. In Drosophila, the Cec genes constitute a multigene family whose members are arranged in tandem. The complete Cec family was isolated in two obscura group species: D. subobscura and D. pseudoobscura. The chromosomal regions encompassing the Cec genes were subsequently sequenced and mapped by in situ hybridization. In D. pseudoobscura, as in species of the D. melanogaster complex and in D. virilis, the Cec genes constitute a single cluster with five genes. In D. subobscura, unlike in the rest of the species, the eight members of the family are split into two clusters located in different parts of the same chromosome. Remarkable differences in levels of divergence were observed between copies in both species. The genomic organization and the phylogenetic relationships among members of this family in the genus Drosophila indicate (i) that the presence of two clusters is the derived state of the family, (ii) repeated gene duplication within species, (iii) nonfunctionalization and loss of some Cec copies, and (iv) the presence of both highly divergent and highly similar copies within species. These features are better explained by the birth-and-death model of molecular evolution, which posits that the high instability of the Cec multigene family in Drosophila is simply determined by the duplication rate and the subsequent loss of duplicated loci.