Rett syndrome is a devastating form of autism spectrum disorders, and it is one of the few in which the underlying genetic cause, mutations on the MeCP2 gene (methyl CpG binding protein 2), has been identified. MECP2 is a methyl-DNA binding protein that is thought to function as a transcriptional repressor and has recently been reported to regulate olfactory receptor expression in an unusual way. In MeCP2 knockout mice olfactory receptor neurons express multiple olfactory receptors, in contrast to the wild type mice where only one olfactory receptor allele is expressed in each neuron. Interestingly, the olfactory receptor alleles that appear coexpressed in the MeCP2 knockout neurons are always members of the same chromosomal cluster. The violation of the "one receptor per neuron" rule provides a robust molecular assay for MeCP2 activity. This assay will be used in a high throughput screen of chemicals that can reverse the molecular consequences of MeCP2 deletion in dissociated olfactory neurons. These compounds could eventually be the basis for a pharmacological treatment of Rett syndrome symptoms.