Crambescidins 816 (1), 830 (2), 844 (3), and 800 (4), a family of complex pentacyclic guanidines linked by a linear ω-hydroxy fatty acid to a hydroxyspermidine, have been obtained by bioassay-guided isolation, involving solvent partition and chromatography on Sephadex LH-20, cyano, and C-18 columns, from extracts of the red, encrusting sponge Crambe crambe (Order Poecilosclerida, Family Esperiopsidae). In assays on board the R/V Garcia del Cid during a 1988 Pharma Mar, S.A., expedition to the Western Mediterranean, extracts of C. crambe were regularly active vs. Herpes simplex virus, type 1 (HSV-1), and cytotoxic to L1210 murine leukemia cells. Compounds 1, 3, and 4 inhibit HSV-1 completely, with diffuse cytotoxicity, at 1.25 μg/well and are 98% effective against L1210 cell growth at 0.1 μg/mL. The crambescidins' pentacyclic guanidine moiety has been isolated only once before, and a hydroxyspermidine unit from a marine source is unprecedented.