We tested in vitro 49 isolates of Chlamydia pneumoniae obtained from 35 children with community-acquired pneumonia against clarithromycin and erythromycin. The children were part of a treatment study comparing the two drugs. Clarithromycin was 2- to 10-fold more active than erythromycin, with a MIC for 90% of strains tested and minimal chlamydiacidal concentration for 90% of strains tested of 0.031 microgram/ml compared with 0.125 microgram/ml for erythromycin. Eight of these children, two of whom were treated with erythromycin and six of whom received clarithromycin, remained culture positive after treatment. We were able to test 21 isolates from these children. All were susceptible to both drugs, and the MICs did not change after therapy.