Genetic studies on the secretion process in gram-negative bacteria have made considerable progress. Within the near future, such studies should lead to a detailed understanding of the important features of signal sequences and how they function. The cloning of the structural gene for an enzyme that cleaves signal sequences from precursors of secreted proteins will allow the genetic characterization of this locus and its function. Finally, the isolation and characterization of mutants that affect components of the cell's secretory apparatus are also under way. These mutants permit the detection of genes and their products that are involved in secretion. A combination of the genetic approaches and in vitro studies should lead to a picture of the details of passage of proteins through a membrane.