BACKGROUND : Tuberculosis is a world-wide problem affecting humans and animals. There is increasing development of resistance of the pathogens to current antimycobacterial agents. Many authors have investigated activities of extracts and isolated compounds from plants. The traditional uses of plants have frequently been the criterion to select plants investigated. In this contribution, we investigate whether plant extracts with very good activity against Escherichia coli may also be active against mycobacteria. METHODS : The antimycobacterial activity of eight South African tree leaf extracts with high activity against Escherichia coli were determined in vitro against Mycobacterium smegmatis, M. fortuitum and M. aurum, using a serial microdilution method. The cellular cytotoxicity was also determined by the MTT assay using Vero monkey kidney cells. The selectivity index was determined by dividing the cytotoxicity of extracts by MIC. RESULTS : The antimycobacterial activity of the extracts ranged from 0.02 to 2.5mg/ml. Mycobacterium smegmatis was more sensitive to the extracts (Average MIC=0.96mg/ml) and Mycobacterium aurum was comparatively resistant (Average MIC=2.04mg/ml). The extracts of Cremaspora triflora had strong antimycobacterial activity with a MIC of 0.05mg/ml that compared reasonably well with that of streptomycin (0.01mg/ml) and rifampicin (0.03mg/ml), p>0.05. Cremaspora triflora had the best selectivity index of 2.87 against Mycobacterium fortuitum. CONCLUSION : The high activity of C. triflora extracts against the fast-growing mycobacteria and good cellular safety is promising. It may be interesting to investigate extracts against pathogenic M. tuberculosis, M. bovis and M. avium cultures and to isolate active antimycobacterial compounds.