Extract: Little information is available on the intracellular consequences of the high intensity illumination with visible light that is commonly used in the treatment of neonatal hyperbilirubinemia. The present study was undertaken to determine whether DNA isolated from human cells growing in culture had undergone structural alterations as a result of exposure to high intensity visible light in the absence of added photosensitizers. Analysis of such DNA on alkaline sucrose gradients revealed a diminution in size after illumination. This structural lesion was repairable when the treated cells were subsequently incubated in the dark. These changes were observed at wave lengths (450 nm) of light identical with those utilized in phototherapy and with total light doses (70.4 kJ/m2) representing only 5% of that received by a newborn infant undergoing phototherapy in our nursery for a 24-hr period (1.3 × 103 kJ/m2). Speculation: In view of the known relationship between DNA-modifying activity and mutagenic and/or carcinogenic potential, the present results suggest that phototherapy is a complex process with an inherent potential for serious long term sequelae.