Antimicrobial susceptibilities of 233 gram-positive and 180 gram-negative strains to two novel bis-indoles were evaluated. Both compounds were potent inhibitors of gram-positive bacteria, with MIC(90) values of 0.004 to 0.5 microg/ml. One bis-indole, MBX 1162, exhibited potent activity against all gram-negative strains, with MIC(90) values of 0.12 to 4 microg/ml, even against high-level-resistant pathogens, and compared favorably to all comparator antibiotics. The bis-indole compounds show promise for the treatment of multidrug-resistant clinical pathogens.