Background With the advent of high throughput genomic and proteomic approaches, the ability to generate data has outstripped the ability to assign biological relevance. Searching the MEDLINE literature database of greater than 14 million entries one-by-one makes establishing biological significance a daunting task. The basic PubMed search window contains a typical single search box for the input of simple keyword combinations. PubMed does allows complex searches using advanced search options, but this requires some knowledge of string search assembly, and an understanding of the PubMed Entrez programming utilities. These are still relatively obscure for many molecular biologists. 1 2 3 4 5 11 12 9 Implementation PubMatrix is a CGI front-end application, which submits queries consisting of search and modifier terms against NCBI's PubMed database and presents the results as a matrix of document hits. Results are stored in a database for retrieval and are presented as hyperlinks to the user for rerunning individual queries of interest. The application runs on an Apache http server using the PERL programming language and a MySQL database for storing terms and results. Results st  th  1 1 1 10 quisquiliarum ineo quisquiliarum egredior Figure 1   2 Figure 2 The report page from a simple search of gene names versus neural modifier terms. All reported numbers are hyperlinked and will initiate a de-novo search for that specific term combination.  1 Table 1 Examples of categorical search lists Category Examples Official Gene Symbols APOB, ACE, BDNF, CD45, ... Polymorphic markers D1S478, D6S470, D13S193, ... DNA sites AAATTT, CAGCAG, TTTTTT, ... Chromosomal bands 1ter*, 1p36*, 1p35*....Xq27*, Xter* Countries sweden, canad*, mexic*, finland, ... Common Prescription drugs acetaminophen, acyclovir, albuterol, alprazolam, ... Common diseases atopic dermatitis, asthma, crohn's, Celiac, Graves',... Date of Publication 1973 [dp], 1974 [dp]......2000 [dp], 2001 [dp], 2002 [dp] Meeting Speakers Weiss A, Pierce SK, Kupfer A,... 3 4 3 4 11 12 Figure 3 Gene expression results (Z-ratio) of cisplatin treatment of an ovarian tumor cell line versus keywords relevant to cisplatin resistance. This graph was constructed in MS EXCEL directly from a PubMatrix search result table using the 3D chart view option after adding gene expression values (Z-ratios).  Figure 4 Visual display of chromosomal-band term list versus the term. "autoimmune". Search terms were 313 sequential human chromosomal bands (1pter, 1p36, 1p35, 1p34, etc....Xq26, Xq27, Xq28, Xqter) versus the single modifier term "autoimmune". This graph was constructed in MS EXCEL using 3D chart view option after separating individual chromosome results into individual columns.  Conclusions PubMatrix allows a simple systematic approach to query the medical literature in PubMed with comparative keyword lists. It performs simple automatic queries and greatly reduces analysis time. In this way, increasingly large datasets generated by high-throughput multiplex assays such as proteomic or microarray assays can be mined, archived, displayed, and annotated for biological and disease relevance. Availability and requirements  Authors' contributions KGB and TJB conceived the approach and participated in early design and testing. DAH, GD, RAL, and CC participated in software design and testing. JE participated in web design, database development, and algorithm modification. All authors read and approved the final manuscript