Calyculins E (5), F (6) G (7). and H (8) were isolated from the marine sponge Discodermia calyx. The structures for 5-8 were assigned on the basis of the interpretation of spectral data. These novel calyculins were potent inhibitors of protein phosphatases 1 and 2A: effective doses for 50% inhibition of protein phosphatases 2A activity for these calyculins were 2.7-6.0 nM.