The resistance rate of 67 Mycoplasma pneumoniae isolates from 356 ambulatory adult patients with respiratory tract infection was 69% (46 of 67). All 46 macrolide-resistant strains harbored point mutations in the 23S ribosomal RNA gene. Patients infected with macrolide-resistant M. pneumoniae required significantly longer durations of antibiotic therapy and had longer time to resolution of fever.