With the completion of the Human Genome Project, our vision of human genetic diseases has changed. The cloning of new disease-causing genes can now be performed in silico, and thousands of mutations are being identified in diagnostic and research laboratories yearly. Knowledge about these mutations and their association with clinical and biological data is essential for clinicians, geneticists, and researchers. To collect and analyze these data, we developed a generic software called Universal Mutation Databases (UMD) to create locus-specific databases. Here we report the new release (September 2004) of this freely available tool (www.umd.be), which allows the creation of LSDBs for virtually any gene and includes a large set of new analysis tools. We have implemented new features to integrate noncoding sequences, clinical data, pictures, monoclonal antibodies, and polymorphic markers (SNPs). Today the UMD retains all specifically designed tools to analyze mutations at the molecular level, as well as new sets of routines to search for genotype-phenotype correlations. We also created specific tools for infrequent mutations such as gross deletions and duplications, and deep intronic mutations. A large set of dedicated tools are now available for intronic mutations, including methods to calculate the consensus values (CVs) of potential splice sites and to search for exonic splicing enhancer (ESE) motifs. In addition, we have created specific routines to help researchers design new therapeutic strategies, such as exon skipping, aminoglycoside read-through of stop codons, or monoclonal antibody selection and epitope scanning for gene therapy.