Clavosines A (1) and B (2), novel metabolites closely related to calyculins and calyculinamides, have been isolated from the marine sponge Myriastra clavosa. Clavosine C (3) was also isolated and is assumed to be an artifact from clavosine B (2). Structures of these compounds were determined by spectroscopic analysis and by comparison of their NMR data with those of the calyculins and calyculinamides. Clavosines A and B were found to be very potent cytotoxins in the National Cancer Institute's screening panel of 60 tumor cell lines and were potent inhibitors of the type 1 and 2A serine/threonine protein phosphatases.