The purpose of this work is to reveal the numbers, effects, and locations of genes causing morphological differences and reproductive isolation among closely related species of Drosophila. Our long-term goal is to understand the process of speciation through the genetic patterns of species differences. Using classical genetic analysis within three well-characterized groups of Drosophila, we will address these questions: 1. Are morphological and behavioral differences among species, and postzygotic reproductive isolation in hybrids, polygenic or due to one or two loci of large effect? 2. Do sex chromosomes play a disproportionate role in the evolution of hybrid sterility and inviability? 3. Does postzygotic isolation occur in a consistent pattern, with the initial evolution of X-chromosomal male sterility and inviability followed by similar anomalies in females? 4. Is the genetic basis of reproductive isolation similar in males and females? 5. Are differences between members of related species pairs within a group caused by similar genetic architectures? 6. Are unusual genetic changes associated with island speciation events? Because a phylogeny of four species in the D. melanogaster group is critical in interpreting our genetic data, we will also perform a phylogenetic study using DNA restriction mapping of at least six sequenced loci in these species. Our data should help distinguish among current theories of speciation and lead to the construction of new ones. The results may also be relevant to understanding the origin of species in many animal groups, including humans.