Four new cytotoxic cyclodepsipeptides, geodiamolides C(3) to F(6), have been isolated from the sponge Pseudaxinyssa sp. collected in Papua New Guinea. The structures of metabolites 3 to 6 have been solved by spectroscopic analysis.Three cyclodepsipeptides, geodiamolide A (1), geodiamolide B (2)1 and iaspamide (7), 2.3 have recently been isolated from the Caribbean sponge Geodia sp. and the South Pacific sponge Jaspis sp., respectively. The depsipeptides 1, 2 and 7 contain a common 12-carbon polypropionate unit and they differ in the amino acid residues found in the tripeptide portion of the macrocycle. All three metabolites were reported to exhibit potent antimicrobial activity against the yeast Candida albicans, 1/2 and iaspamide (7) was also reported to be insecticidal2a,2b and cytotoxic.2b Interest in the biological activities of these depsipeptides has stimulated the total synthesis of 1.4 25a and 7.5b In our continuing search for antineoplastic metabolites from marine invertebrates.6,7 we have discovered that crude extracts of the sponge Pseudaxinyssa sp.8 collected in Papua New Guinea exhibit in vitro cytotoxicity (L1210 ED50 <1 µg/mL)), in vivo antineoplastic activity (P388 T/C 153 % @ 50mg/Kg) and in vitro antimicrobial activity (against C. albicans). Bioassay guided fractionation of the crude extracts led to the isolationof the two known mtabolites, gecdiamolides A (1) and B (2), and the four new metabolites, geodiamolides C (3) to F (6). The structures of the iew metabolites 3 to 6 are reportad below.