We are interested in knowing how cells of a single organism can differentiate to form specific tissue types. We have chosen to address one aspect of the question by learning how one gene, the cut locus of Drosophila melanogaster, is expressed differently in different tissues of the fly. We have now cloned DNA sequences representing the entire gene, which encompasses 200 kb or more of DNA. A large number of mutants have been analyzed. We find that the deletion of sequences in the leftmost part of the gene cause phenotypic effects primarily in the legs, while deletion of or insertions into sequences slightly to the right cause effects primarily in the wings. Mutations in a 70 kb to the right affect the wings, head, and thorax and cause lethality. A fourth group of mutations lacks cut locus function in all tissues. These mutations map at the rightmost end of the gene. The availability of tissue specific mutants of a gene afford the opportunity to experiment to find out how the gene normally operates in tissue specific ways. We are currently studying the transcriptional activity of the cut locus to find out how the tissue specificity of the mutant phenotypes relates to the transcriptional activity of the gene. We now know that many of the cut mutants are insertions of retrovirus-like sequences into the cut locus DNA, and we are interested in understanding the affect of these sequences on gene activity. Some of these mutations are suppressible and will be useful in determining how a mutation caused by a retrovirus-like sequence can be suppressed.