Although Rocky Mountain spotted fever is the most common fatal tick-borne disease in the United States, it remains relatively rare. In this survey of 1999 children living in the southeastern and south central United States, 12% of children had Rickettsia rickettsii titers of at least 1:64. There was a strong relationship between increasing age and seroprevalence at each cutoff titer. Seroprevalence also varied with location, from 3.5% in Louisville, Ky, to 21.9% in Little Rock, Ark. These data suggest that infections with R rickettsii may be common and subclinical, and they point out the limited usefulness of single-antibody titers in diagnosing Rocky Mountain spotted fever.