Normal human lymphocytes in culture were stimulated by the addition of phytohemagglutinin, and deoxyribonucleic acid (DNA) synthesis was measured by the incorporation of tritiated thymidine. The effect of 11 commonly used antibiotics on DNA synthesis then was measured by adding each antibiotic to the culture in concentrations ranging from 2 to 64 microng/ml, a range which covers the plasma levels obtained during customary clinical therapy. Severe dose-dependent suppression of DNA synthesis was found in the presence of two preparations of minocycline, oxytetracycline, and the ascorbic acid salt of tetracycline. Less severe but stil significant suppression was found in the presence of chloramphenicol, clindamycin, tetracycline, and ascorbic acid alone. No effect was noted when penicillin, carbenicillin, or cephalothin was added, and slight stimulation was found in the presence of gentamicin. It is postulated that these findings may help to explain fungal and viral superinfection following antibiotic therapy and that they may play a role in the failure of antibiotic therapy to eliminate some infections.