Motivation: Almost all users encounter problems using sequence analysis programs. Not only are they difficult to learn because of the parameters, syntax and semantic, but many are different. That is why we have developed a Web interface generator for more than 150 molecular biology command-line driven programs, including: phylogeny, gene prediction, alignment, RNA, DNA and protein analysis, motif discovery, structure analysis and database searching programs. The generator uses XML as a high-level description language of the legacy software parameters. Its aim is to provide users with the equivalent of a basic Unix environment, with program combination, customization and basic scripting through macro registration. Results: The program has been used for three years by about 15000 users throughout the world; it has recently been installed on other sites and evaluated as a standard user interface for EMBOSS programs. Availability: The program is freely available over the Internet at the following URL: http://www.pasteur.fr/~letondal/Pise/. Contact: pise@pasteur.fr