A complete system containing high density microarrays on glass slides and all necessary experimental reagents has been developed. Utilizing the TSA™ (Tyramide Signal Amplification) technology, the system offers significantly improved sensitivity which reduces sample requirement by 10-50 fold and uses fluorescence-based detection. MICROMAX™ Microarray System I spotted with 2,400 known human genes provides the opportunity to monitor gene expression between two comparative cell lines or tissue samples. In addition to following global changes in gene expression patterns in basic research, the system also offers the potential of detecting changes in gene expression for diagnostic applications. We have used the system to analyze gene expression in human postmortem brains. Samples of parietal cortex of patients with Rett syndrome, an autism-related disease that affects females exclusively, were compared to age-matched tissue samples from normal controls. Several genes were up- or down-regulated in the diseased samples. These studies highlight the potential of the MICROMAX™ system to measure gene expression in complex biological samples.