The comparative efficacy of doxycycline versus amoxicillin, cephalexin, cefaclor and enoxacin was examined in four separate cross-over and blinded studies of acute bacterial bronchitis in chronic bronchitis and asthma. The efficacy of doxycycline over the eleven-year period (1975-1986) covered by these studies also was examined. Patients with acute bacterial exacerbations, defined by increased chest symptoms, increased bacteria and sputum neutrophilia, were randomly entered. When a new acute infection occurred, they were re-entered and received the other antibacterial. Response was recorded as successful or not; early rebound infections and the periods free of infection were noted. A total of 136 exacerbations were evaluated in the comparison of doxycycline with the other 4 antibacterials, and 93 exacerbations in the long-term efficacy of doxycycline. The acute success was similar for doxycycline with the other antibacterials and was superior to cefaclor. Early rebound infections occurred less frequently with doxycycline as compared to the cephalosporins and was similar versus amoxicillin and enoxacin. The infection-free period was longer after doxycycline than with the other four antimicrobials. Doxycycline maintained its efficacy to elicit a prompt response and provide a long infection-free period, but an increase of early rebound infections was noted over the eleven-year period.