Hexane extracts of Hypericum drummondii showed significant activity against the Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, and the acid-fast bacterium Mycobacterium smegmatis in an agar well diffusion assay. Employing bioassay-directed fractionation procedures, four new rottlerin-type compounds (drummondins A, B, C[1-3], and F [4]) were isolated and identified by spectral and physical characterization. The antimicrobial activity of these compounds was comparable to or greater than that demonstrated by streptomycin and generally correlated with cytotoxic activity determined with cultured P-388, KB, or human cancer cell lines (breast, colon, lung, melanoma). No cell-type selectivity was observed. In addition, two known compounds, albaspidins A-A [5] and P-P [6], were isolated and structured characterized. Neither demonstrated appreciable antimicrobial or cytotoxic activity.