Immunoglobulin A (IgA) antibodies reactive with Streptococcus mutans MT3 cells (serotype c) were sought, using an indirect enzyme-linked immunosorbent assay, in the saliva of humans who either harbored or did not harbor detectable levels of this organism. Samples of unstimulated whole saliva from three adults and one child who were infected with S. mutans contained IgA which bound to MT3 cells. Saliva samples of two adults studied also contained IgA which reacted with S. mutans strains of serotypes e, g, a, and b, the latter two of which are rarely isolated from humans. The saliva of three children who did not harbor detectable levels of S. mutans and of three of five predentate infants also contained IgA reactive with MT3 cells. The latter observation is of special interest since S. mutans does not colonize the mouth before eruption of teeth. Thus, the presence of salivary IgA reactive with S. mutans cells is not necessarily related to present or past infection by this organism. Absorption with MT3 cells markedly reduced the reactivity of adult saliva without greatly altering the total concentration of IgA present; this suggests that the IgA was not binding to S. mutans MT3 cells via Fc receptors. The possibility that the antibodies which reacted with S. mutans MT3 may have been induced to other bacteria with cross-reactive antigens was supported by the finding that absorption of saliva with mixed bacterial growth derived from common dairy products significantly reduced its reactivity. Absorption experiments further suggested that a significant portion of the salivary IgA antibodies was binding to glucans on the cell surface.