It has been proposed that recurrent aphthous ulceration (RAU) is caused by hypersensitivity to oral streptococci. This hypothesis is based on reports that RAU patients have increased levels of circulating IgG antibodies against oral streptococci, and that rabbit antisera prepared against oral streptococci are cross-reactive with oral mucosa. Using indirect immunofluorescence, we have investigated both of these reported phenomena. End-point titers of serum antibodies against three different strains of oral streptococci were assayed from nine RAU subjects with active ulcers and compared with those of nine control subjects. Titers ranged from 1:2 to 1:64 in both groups and do not appear to have any clinical or immunopathogenic significance. Cross-reactivity was studied using hyperimmune rabbit antisera raised against five different strains of oral streptococci. Homologous bacterial titers ranged from 1:1024 to 1 :8192, but none of these anti-streptococcal sera produced heterologous titers greater than 1:32 with oral mucosa. This apparent low level of cross-reactivity with oral mucosal antigens appears to be non-specific and clinically insignificant. In previous reports, we have used both leucocyte migration and lymphocyte blast transformation to study cell-mediated immunity to viridans streptococci in RAU (Gadol et al., 1985; Greenspan et al., 1985). None of our results supports an immunopathogenic role for oral streptococci in RAU.