Genes involved in the determination and differentiation of adult tissues in Drosophila melanogaster have been identified by genetic interactions with homeotic and segmentation genes already known to be required in these tissues. Many new genes required for transcriptional activation of developmental genes have been identified. One of these new genes, brahma, encodes a large nuclear protein conserved from yeast to man. brahma mutations have in turn been used to identify other interacting genes required for transcriptional activation. The osa gene, which shows allele-specific interactions with brahma mutations, has been cloned and encodes a single 3 kb transcript. We have shown that maternal expression of both brahma and osa is essential for early embryogenesis, while zygotic expression of both is essential late in embryogenesis and during larval growth. We have also identified a third gene [the Pearl gene] that may encode a protein that interacts with both brahma and osa proteins. We have isolated and characterized a cis-regulatory mutation in the Drosophila hedgehog gene. The hedgehog gene encodes a secreted protein that is involved in cell-cell signalling during both embryonic segmentation and adult patterning. Our cis-regulatory hedgehog mutation derepresses transcription in larval cells that normally do not express hedgehog proteins, and the misexpression of hedgehog proteins causes neighboring cells to alter their developmental fates. We have used the phenotypes caused by hedgehog misexpression to isolate interacting mutations. These interacting mutations identify genes that are required for hedgehog expression or function. We have mapped twenty-four of these mutations to seven genes that are also required for homeotic gene transcription. These seven genes include the brahma, osa, trithorax, and moira genes that we have extensively characterized.