The incidence of Lyme disease in most endemic areas is unknown but will be an important factor in determining the cost-effectiveness of Lyme disease vaccines in those areas. The authors developed a deterministic model with nine components to estimate the frequency of Ixodes scapularis tick bites and the resulting incidence of Lyme disease in residents of endemic areas. For each component, best point estimates and plausible ranges of values were based on the published literature, unpublished data, expert opinion, or a combination of the above. By using the mean, crude, annual total of 3,827 Lyme disease cases reported from the endemic county of Westchester, New York, in 1991-1994, a mean of 178,889 I. scapularis bites (20.4 per 100 person-years) and a mean of 10,632 incident Lyme disease cases (1.2 per 100 person-years) were estimated to have occurred per year. Results of a sensitivity analysis that used two different methods suggested that this deterministic model is reasonably robust. In conclusion, according to this model, the incidence of Lyme disease in Westchester County is several-fold higher than suggested by the current passive reporting system.