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A spectrophotometric method has been developed for the rapid measurement of the antimicrobial activity of natural products, including crude extracts or pure materials. The assay depends on the measurement of non-specific esterase activity using fluorescein diacetate (FDA) hydrolysis in broth cultures of microbes after they have been treated with test compounds. The assay is accurate, reproducible and economical in both time and materials. The speed and economy of the method make it suitable for the rapid screening of many samples and the bioassay directed purification of antimicrobial substances. The assay can also be used with a wide variety of micro-organisms since most micro-organisms are FDA positive. Applications are described in the fields of marine natural products chemistry and essential oils research.