Short-term photochemical insult of cultured rat lenses caused by the generation of H2O2, O2<--and OH. was found to lead to rapid irreversible damage to the epithelial cell layer. This irreversible damage was measured by Trypan blue staining, terminal deoxyribonucleotidyl transferase labeling, DNA laddering and morphological analyses. There appears to be an inverse relationship between the period of photochemical insult and the post-insult time required to observe epithelial cell damage. Insulting periods of a few hours require post-insult intervals of days to observe significant cell damage and weeks before complete cortical cataracts are found. Epithelial cell damage precedes the loss of transparency.