A model (LYMESIM) was developed for computer simulation of blacklegged tick, Ixodes scapularis Say, population dynamics and transmission of the Lyme disease agent. Borrelia burgdorferi Johnson. Schmid, Hyde, Steigerwalt & Brenner, LYMESIM simulates the effects of ambient temperature, saturation deficit, precipitation, habitat type, and host type and density on tick populations. Epidemiological parameters including host infectivity, tick infectivity, transovarial transmission, and transstadial transmission are included in the model to simulate transmission of the Lyme disease spirochete between vector ticks and vertebrate hosts. Validity of LYMESIM was established by comparing simulated and observed populations of immature I. scapularis on white-footed mice. Peromyscus leucopus, (Rafinesque), at 2 locations in Massachusetts. Validity also was indicated by comparisons of simulated and observed seasonality of blacklegged ticks in New York, Massachusetts, Florida, and Oklahoma-Arkansas. Further model validity was shown by correlation between simulated and observed numbers of immature ticks engorging on white-footed mice at 3 sites in Massachusetts. The model produced acceptable values for initial population growth rate, generation time, and 20-yr population density when historical meteorological data for 16 locations in eastern North America were used. Realistic rates of infection in ticks were produced for locations in the northeastern and northcentral United States. LYMESIM was used to study the effect of white-footed mouse and white-tailed deer, Odocoileus virginianus (Zimmerman), densities on tick density and infection rates. The model was also used to estimate tick density thresholds for maintenance of B. burgdorferi.