The cold waters of Antarctica are known to harbor a rich biodiversity. Our continuing interest in the chemical analysis of Antarctic invertebrates has resulted in the isolation of friomaramide (1), a new, highly modified hexapeptide, from the Antarctic sponge Inflatella coelosphaeroides. The structure of friomaramide was determined using spectroscopic methods and its configuration established by Marfey's method. Friomaramide, which bears the unusual permethylation of the amino acid backbone and is the longest polypeptide bearing a tryptenamine C-terminus, blocks >90% of Plasmodium falciparum liver-stage parasite development at 6.1 μM.