In studies of Lassa fever in Sierra Leone, the prevalence of human antibody to Lassa virus ranged from 8% to 52%. Mastomys natalensis, the reservoir of Lassa virus, constituted 50%-60% of the rodents captured in houses but only 10%-20% of those captured in surrounding agriculture and bush areas (chi 2 = 90.2, P less than 10(-6), df = 1), a finding suggesting that houses are the most-important location for transmission of Lassa virus. Viral infection of Mastomys from houses ranged from 0% to 80%. The incidence of seroconversions in susceptible persons ranged from 5% to 22% per year; the ratio of illness to infection ranged from 9% to 26%, and the proportion of febrile illness associated with seroconversion was 5%-14%. Eightfold rises in titer of antibody occurred in 1%-18% of the antibody-positive population, a result suggesting reinfection. We estimate the ratio of fatalities to infection to be 1%-2%, a rate lower than estimates based on hospitalized cases. The high incidence of Lassa fever makes it a major problem in West Africa.