Mammary gland involution follows the cessation of lactation. Similar to lactogenesis, the involution process requires an ordered sequence of events including the termination of milk production, increased secretion of lactoferrin, apoptosis of the mammary epithelium and remodelling of the extracellular matrix of the gland. A completed cycle of involution requires apoptosis of the epithelial mammary structures involved in milk production, resulting in the loss of the milk-secreting alveoli as the gland returns to a pre-pregnant state. The complex cellular remodelling and cell-specific targeted apoptosis make mammary involution an excellent model system to apply to microarray platforms. The development of a 3K mammary-enriched mouse cDNA microarray has enabled us to perform high-throughput hybridization analysis to establish the gene expression profiles associated with the distinct cellular stages of the involution process. We find that a fall in anti-apoptosis genes appears to initiate the process, followed by induction of stress-response genes. In addition to uncovering many genes involved in cell-cycle regulation, apoptosis, DNA repair and cytoskeletal remodelling, these microarrays have proven to be a powerful tool for gene discovery in epithelial involution.