The antimicrobial activity of the phenothiazine derivatives thioridazine and prochlorperazine have been evaluated with 11 Enterococcus faecalis strains and 9 Enterococcus faecium strains, originating from human infections and animal faecal flora. We found that all E. faecalis and E. faecium strains, regardless of their susceptibility to commonly used antibiotics, were inhibited by thioridazine at a concentration of 16-32 microg/ml and by prochlorperazine at a concentration of 32-64 microg/ml. Combinations of the antibiotics vancomycin or ampicillin and thioridazine and prochlorperazine at subinhibitory concentrations, could render vancomycin- or ampicillin-resistant bacteria sensitive to each of the antibiotics. Verapamil and reserpine, inhibitors of P-glycoprotein-mediated multidrug resistance, did not reduce resistance. Our results outline modification of resistance in enterococci induced by phenothiazine derivatives unrelated to P-glycoprotein-mediated multidrug resistance.