The aim of this study was to determine the relative role of apoptosis in photodynamically-induced cytotoxicity or radiation-induced cytotoxicity for hepatoma and lymphoma cells. Human hepatoma cells and mouse lymphoma cells were treated with either photodynamic therapy (PDT) or ionizing radiation. Dosimetry studies of immediate cell death following photodynamic therapy in the hepatoma cell line demonstrated second-order kinetics, similar to that seen in the lymphoma cells. No immediate cell death was noted in the hepatoma or lymphoma cells following ionizing radiation, but experiments measuring delayed cell death demonstrated a dose-dependent response. Maximum DNA ladder formation occurred 2 hr after PDT and 24 hr after ionizing radiation in the lymphoma cells, which was consistent with the time courses of cell death for these treatments. The hepatoma cell line did not demonstrate DNA ladder formation despite dosages of PDT or ionizing radiation sufficient to cause high levels of cytotoxicity. © 1994 Plenum Publishing Corporation.