During the first quarter of the 20th century, massive rat-borne plague epidemics occurred in port cities of the United States in conjunction with the last world-wide pandemic which originated in China in 1893. By 1950, plague was found to be firmly established in wild rodent populations in states west of the 100th meridian. Presumably because of improved sanitation coupled with retreat of the world-wide pandemic, there have been no human cases in this country associated with urban rats since 1924. However, sporadic cases, fewer than 10 per year, are reported as due to contact with wild rodents, lagomorphs, rural rats, and/or their fleas. Recent observations suggest that: a) in the current decade there has been an increase in human plague cases; b) there continues to be a serious potential of a single undiagnosed and untreated case, which possibility is intensified by the very paucity of human cases decreasing the likelihood of a correct diagnosis and by changing patterns of life exhibited by members of our society (e.g., hippie communes and a generally increased mobility); and c) the apparent distribution of plague only in the area west of the 100th meridian might be found to represent an unrealistic generalization if adequate surveillance were carried out. At the present time human plague cases from wild animal sources tend to be isolated events both spatially and temporally and often cannot be attributed to confined and definable epizootic sources amenable to effective control programs. Improved means for epizootic control and long-term management of enzootic plague sources must be sought aggressively. These measures should include development of: a) a surveillance network to detect plague activity in rodent and lagomorph populations throughout the western United States; b) effective, yet ecologically sound, means of ectoparasite control, including suitable materials and methods of application; c) methods for management of plague-susceptible wild animal populations, particularly where they exist in contact with high use recreation and residential areas; and d) more extensive knowledge of enzootic plague and the factors that bring about epizootic plague and potential human contact.