The activity of doxycycline and tetracycline against natural strains of the plague microbe of different origin was studied in vitro. The MICs of doxycycline and tetracycline for the majority of the strains were 0.8 and 3.2 micrograms/ml respectively. The efficacy of doxycycline and tetracycline in the prophylaxis and treatment of experimental plague infection was studied comparatively on albino mice. Doxycycline proved to be superior to tetracycline. By using short-term schemes of the treatment and longer intervals between the drug administrations it was shown that doxycycline had a prolonged action. Moreover, the injectable doxycycline was found to be superior to the oral one. The high efficacy of doxycycline in the treatment of the albino mice with experimental plague infection was confirmed by the pathohistological findings. The pathomorphological changes in the animals were limited by local affections in the site of the contamination and the regional lymph nodes followed by the development of infiltration foci.