The Pacific Symposium on Biocomputing (PSB 2004) is an international, multidisciplinary conference for the presentation and discussion of current research on the theory and application of computational methods in problems of biological significance. The rigorously peer-reviewed papers and presentations are collected in this archival proceedings volume. PSB is a forum for the presentation of work on databases, algorithms, interfaces, visualization, modeling and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology. PSB 2004 brings together top researchers from the US, the Asia-Pacific region and the rest of the world to exchange research findings and address open issues in all aspects of computational biology.