Eighty healthy men with nasal carriage of coagulase-positive staphylococci were given cloxacillin, rifampin, cloxacillin plus rifampin, or no drug. Treatment with rifampin alone or with rifampin plus cloxacillin eradicated the original strain from 80% of the men for 12 weeks after treatment; 15%-20% of the 80 subjects acquired a strain of a different phage type. Treatment with cloxacillin alone did not significantly alter the rate of carriage. Only one of 40 men receiving rifampin (either alone or with cloxacillin) acquired rifampin-resistant, coagulase-positive staphylococci; seven of the 40 acquired rifampin-resistant, coagulase-negative staphylococci. Rifampin-resistant organisms did not persist in repeat nasal cultures five months after treatment. Of the 40 subjects given rifampin alone or rifampin plus cloxacillin, 60% had repeat nasal cultures done one year later. Only 50% were found to be carriers of coagulase-positive staphylococci. In another study, coagulase-positive staphylococci were eradicated from 70% of 20 carriers undergoing renal dialysis who received rifampin plus cloxacillin.