Human plague occurs most commonly when fleas infected with Yersinia pestis (Y pestis) bite humans. Worldwide on average for the past 50 years 1,700 cases have been reported every year. In the United States, 390 cases were reported from 1947 to 1996. Plague has caused the death of as much as 60 percent of regional populations since AD 541, but advances in living conditions, public health and antibiotic therapy make future pandemics improbable. However, plague outbreaks from biological terrorism are a plausible threat. In 1970, the World Health Organization reported that, in a worst-case scenario, if 50 kilograms of Y pestis were released as an aerosol over a city of 5 million, pneumonic plague could occur in as many as 150,000 people, 36,000 of whom would die. Aerosol dispersion is the most likely international dissemination of plague. Outbreak symptoms, occurring one to six days after exposure, would initially resemble those of other severe respiratory illnesses. People would die quickly after onset of symptoms. Historically, the preferred treatment for plague has been streptomycin, but modest supplies are available. Tetracycline, doxycycline and gentamicin also have been used successfully. Once it is suspected pneumonic plague cases are occurring, anyone with fever or cough should be immediately treated with antimicrobials. Delaying therapy until confirmation testing is completed would decrease survival. Children should receive streptomycin or gentamicin. Pregnant women should receive gentamicin or doxycycline, if the former is not available. Asymptomatic people in close proximity to others with pneumonic plague should receive antibiotics for seven days and watch for fever or cough. They should also wear surgical masks, gowns, gloves or other items that would protect against infected respiratory droplets. References, tables