The immune response to Kingella kingae was determined by enzyme-linked immunosorbent assay, using outer-membrane proteins as coating antigen, in 19 children with invasive infection. The age-related incidence of K. kingae disease in southern Israel during 1988-2002 was calculated and correlated with serum antibody levels in healthy children. Significant increases in immunoglobulin G (IgG) levels were found in children convalescing after invasive infections. The incidence was 1.3, 40.3, 23.9, 5.7, and 1.9 cases/100,000 children among those aged 0-5, 6-11, 12-23, 24-35, and 36-47 months, respectively. A low attack rate and undetectable serum IgA and high IgG levels were found during the first 6 months of life, which indicates that protection was conferred by maternally derived immunity. The high attack rate found among 6-24-month-old children coincides with the age at which antibody levels were lowest. Low incidence of disease and increasing antibody levels were found among older children, which probably represents cumulative experience with K. kingae antigens via colonization or infection.