Abstract In the past several years, oligonucleotide microarrays have emerged as a widely used tool for the simultaneous, non-biased measurement of expression levels for thousands of genes. Several challenges exist in successfully utilizing this biotechnology; principal among these is analysis of microarray data. An experiment to measure differential gene expression can consist of a dozen microarrays, each consisting of over a hundred thousand data points. Previously, we have described the use of a novel algorithm for analyzing oligonucleotide microarrays and assessing changes in gene expression [J. Mol. Biol. 317 (2002) 225]. This algorithm describes changes in expression in terms of the statistical significance ( S-score) of change, which combines signals detected by multiple probe pairs according to an error model characteristic of oligonucleotide arrays. Software is available that simplifies the use of the application of this algorithm so that it may be applied to improving the analysis of oligonucleotide microarray data. The application of this method to problems of the central nervous system is discussed.