Expression levels of 767 genes were measured in HepG2 cells at eight time-points (0,0.5, 1, 6, 12, 16, 20, and 24 hrs) following exposure to the oxidizing agent, diethyl maleate (DEM). DEM treatment caused an immediate and sustained loss of intracellular GSH, with a concomitant increase in GSSG. From 6-12 hours after exposure, there was a substantial increase in the percentage of cells undergoing S-phase arrest and apoptosis. Expression profiles of approximately 90% of the genes fell into one of five clusters generated using hierarchical-clustering software, indicating the well-ordered nature of the stress response. The directional movement and timing of induction for many genes matched closely the known physiological role of the proteins they encode. Inhibitors of the cell cycle (CDKN1, CDKN4D, ATM) were induced while cyclins (PCNA, Cyclin A, Cyclin D1, Cyclin K) were down regulated during the period from 6-20 hours. Likewise, pro-apoptotic genes such as the caspases (CASP9, CASP3, CASP2) and APAF were induced during the same period. Results of this study indicate that there is a good correlation between time-dependant physiological, biochemical, and gene expression data.