The roles of three homeotic genes, Ubx+, Scr+, and Antp+, in the Drosophila thorax have been studied by determining the cellular phenotypes of mutations resulting in loss of gene function. The principal results are: (i) The Scr+ and Ubx+ genes are required in the prothorax and metathorax, respectively; in the absence of these genes, both segments develop like the mesothorax. (ii) The Antp+ gene is required in all three thoracic segments: in its absence, parts of the mesothorax are transformed into corresponding parts of the antenna, and similar transformations to antenna are found in the prothorax and metathorax if the Scr+ and Ubx+ genes also are absent. (iii) Loss of the Ubx+ gene early in embryogenesis, but not later, leads to the inappropriate activity of the Scr+ gene in the meso- and metathorax. Results i and ii argue strongly that segmental determination is specified in a combinatorial fashion in the head and thorax by the selective activities of the Scr+, Ubx+, Antp+, and putative head-determining genes. Result iii suggests that a product of the Ubx+ gene also plays an early, regulatory role in ensuring the correct spatial expression of the Scr+ gene during subsequent development.