Our continuing search for bioactive metabolites from Porifera yielded five sesquiterpene isothiocyanates (epipolasin-A through -E) and two thiourea derivatives (epipolasinthiourea-A and -B) from the marine sponge Epipolasis kushimotoensis. The structures of epipolasin-A, epipolasin-B, epipolasinthiourea-A, and epipolasinthiourea-B were elucidated based on chemical and spectral evidence. Three other sesquiterpene isothiocyanates (epipolasin-C, -D, and -E) were isolated as minor components, and their structure elucidation is in progress. The thiourea derivatives epipolasinthiourea-A (14) and -B (15) showed moderate in vitro cytotoxic activities against L1210 cells with ED50 values of 4.1 μg/ml and 3.7 μg/ml, respectively, while epipolasin-A through -E did not exhibit significant bioactivities (e.g., antibacterial, antiviral, and cytotoxic activities in vitro).