The in vitro activity of various tetracyclines and antimalarials alone and in combinations against 20 clinical isolates of Escherichia coli was investigated. The minimum inhibition concentration of the tetracyclines ranged from 1.2 to 160 μg/ml. Demeclocycline was the highest in activity. The antimalarials were ineffective. Variable percentage of strains responded to the synergistic effect of the various antibiotics-drugs combinations. Strains which are relatively insensitive to the tetracyclines did not respond to the synergistic effect of the combinations. The bactericidal effect of the combinations was shown by the enhanced rate of killing that occurred at 6 h. Synergism was reversed by divalent cations