Kalihinene and isokalihinol B. cytotoxic diterpene isonitriles have been isolated from the marine sponge Acanthclla klethra. Structures of these compounds were elucidated by interpretation of NMR spectra as well as by single crystal X-ray diffraction. Marine sponges of the order Halichondrida often contain sesquiterpene isonitriles and diterpene isonitriles which show a broad spectrum of biological activities, including antimicrobial and ichthyotoxic properties. 2 In our screening for antifungal and cytotoxic metabolites in Japanese marine invertebrates, the marine sponge Acanthella klethra collected during the cruise on the R/V Toyoshio-maru of Hiroshima University in Kuchinoerabu Island of the Satsunan Archipelago (-10 to -15 m) showed marked activity in both assays. Bioassay-guided fractionation of the ethanol extract of the sponge yielded two new diterpene isonitriles, named kalihinene (1) and isokalihinol B (2) along with the known diterpene kalihinol A (3). This paper deals with the isolation and structure elucidation of these substances.