The cytotoxicity-guided fractionation of the MeOH extract of Oldenlandia diffusa (Rubiaceae) led to the isolation of ursolic acid (UA) as an active principle. Ursolic acid demonstrated a significant inhibition of the proliferation of cultured tumour cells, i.e. A549 (human lung), SK-OV-3 (ovary), SK-MEL-2 (skin), XF498 (brain), HCT-15 (colon), SNU-1 (stomach), L1210 (murine leukaemia) and B16-F 0 (murine melanoma). A marked increment of T/C (b200%) was also observed when UA was administered to mice bearing sarcoma-180 cells. The microscopic analyses (phase contrast microscope and TEM) of SNU-1 cell after continuous exposure to UA for 4 and 24 h showed typical morphological changes of the cell due to an apoptotic effect. The nucleosomal DNA of HL60 cells pretreated with UA was cleaved into several oligomeric fragments which was due to a typical apoptotic effect. However, the in vitro cytotoxic effect of UA on tumour cells was decreased in a dose dependent manner by the addition of nicotinamide, a poly-(ADP-ribose) polymerase inhibitor, or aurin tricarboxylic acid (ATA), an endonuclease inhibitor. These results suggested that the cytotoxicity of UA or the apoptotic effect of UA on tumour cells might be related to the activation of the endonucleolytic enzyme and subsequent activation of poly(ADP-ribose) polymerase in tumour cells and these could eventually lead to cell lysis.