Three nematicidal cardenolides were obtained from the AcOEt extract of Nerium indicum Mill. by bioassay-guided fractionation. They include a new compound, 3beta-O-(beta-D-diginosyl)-14,15alpha-dihydroxy-5alpha-card-20(22)-enolide (1), and two known compounds, uzarigenin (2) and cardenolide N-1 (3). The median lethal concentrations (LC(50)) of compounds 1-3 against the nematodes Bursaphelenchus xylophilus, Panagrellus redivivus, and Caenorhabditis elegans at 72 h were 103.3, 49.0, and 45.4 mg l(-1), 257.0, 62.7, and 177.8 mg l(-1), and 242.9, 29.1, and 41.7 mg l(-1), respectively. This is the first report about the nematicidal activity of cardenolides.