Helichrysum cymosum, an aromatic plant used in traditional medicine to treat respiratory ailments and wound infections is widely distributed throughout Southern Africa. Using bioassay-guided fractionation, an active compound was isolated using column chromatography and identified as the known phloroglucinol derivative, helihumulone (1). The antimicrobial activity (MIC), antimalarial (tritiated hypoxanthine incorporation) and toxicity (tetrazolium-based cellular viability assay) profiles were determined for the essential oil, acetone extract and helihumulone (1). The MIC ranges for essential oil, acetone extract and helihumulone (1) were 1-8, 0.078-0.313 and 0.016-0.125 (mg/ml) respectively. While the acetone extract was at least six times more active than the essential oil in the antimicrobial investigation, the antimalarial studies indicated that the essential oil was most active against the chloroquine-resistant Plasmodium falciparum FCR-3 strain (IC50 value: 0.204 +/- 0.05 Ag/ml). It was however, also the most toxic (IC50 value: 17.47 +/- 3.14 Ag/ml). The GC/MS analysis of the essential oil is also presented.