Marine micro-organisms represent an under explored resource for the discovery of novel antiviral agents. Here, we describe a series of peptides designated halovirs A-E (1-5) that are produced during the saline fermentation of a marine-derived fungus of the genus Scytalidium. These lipophilic, linear peptides are potent in vitro inhibitors of the herpes simplex viruses 1 and 2. Evidence is presented that the halovirs directly inactivate herpes viruses, a mechanism of action that could be applicable in the prevention of HSV transmission. The total structures of these new compounds were established by a combination of spectral and chemical techniques. Salient structural features of the halovir hexapeptides include a nitrogen terminus acylated by myristic (C14) or lauric (C12) acid, an unusual Aib-Hyp dipeptide segment, and a carboxyl terminus reduced to a primary alcohol. A qualitative analysis of the secondary structures of these molecules using variable temperature NMR experiments and NOE analyses is also reported.