Hexane extraction of dried, pulverized leaves from the Australian plant Melicope sessiliflora followed by a bioassay-guided fractionation of the extract led to the isolation of three novel isomeric phloroglucinols with inhibitory activity against herpes simplex virus types I and II in vitro. The major active component, sessiliflorene, was shown to have the structure 1 by a combination of mass spectrometry and NMR methods. The two other bioactive isomers, sessiliflorols A and B, were resolved by HPLC whereupon the former crystallized. The structure of sessiliflorol A was determined as 2 by X-ray crystallography and the B isomer was shown to have structure 3 by spectroscopic comparison with 2. Biosynthetic relationships between the three naturally occurring isomers are also proposed.