A Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula yielded two new and toxic natural products, hermitamides A (1) and B (2). The hermitamides were isolated using a brine shrimp (Artemia salina) toxicity assay. Planar chemical structures of 1 and 2 were established through 1D and 2D NMR, as well as FABMS data. Semisyntheses of hermitamides A (1) and B (2) were achieved by coupling the acid chloride derivative of 7(S)-methoxytetradec-4(E)-enoic acid (4), obtained from the same cyanobacterium collection, and the respective free amines, phenethylamine and tryptamine. Hermitamides A (1) and B (2) exhibited LD(50) values of 5 microM and 18 microM in the brine shrimp bioassay, and an IC(50) values of 2.2 microM and 5.5 microM to Neuro-2a neuroblastoma cells in tissue culture, respectively. Hermitamide A was mildly ichthyotoxic to goldfish, with an LD(50) value of 19 microM, while hermitamide B was inactive at 25 microM.