We tested the in vitro activity of clarithromycin, azithromycin, roxithromycin, erythromycin, doxycycline, and tetracycline against 50 clinical isolates of Chlamydia trachomatis. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined in a tissue culture system using cycloheximide treated McCoy cells. MIC values for all the isolates were < or =0.015 microg/ml for clarithromycin, < or =0.125 microg/ml for roxithromycin and azithromycin, and < or =0.25 microg/ml for erythromycin and doxycycline. Almost half of the isolates (44%) were inhibited only by a concentration of 0.5 microg/ml of tetracycline. MBC as high as 4 microg/ml was displayed by doxycycline and tetracycline against 8% and 4% of the isolates respectively of the agents recommended by the Center for Disease Control as drugs of choice for the treatment of chlamydial infections, azithromycin exhibited a markedly better in-vitro activity than did erythromycin and doxycycline.