abstract—Cell‐mediated immunity (CMI) and humoral immunity (HI) against oral bacteria (Streptococcus sanguisstrain 2A, ATCC 10556,Streptococcus sanguisgroup H1,Neisseria subflavaandStaphylococcus) and adult human oral mucosa (AHOM) antigens were investigated in relation to exacerbation of recurrent aphthous stomatitis (RAS). The material consisted of 10 patients with RAS and 10 controls. The CMI and HI were assessed by means of the leukocyte migration test (LMT) and a double‐layer immunofluorescence (IF) technique. Compared with normal controls the leukocyte migration inhibition againstStrep. 2Aand AHOM was significantly increased in patients with exacerbation of RAS and the reactivity seemed to develop in relation to the exacerbation of RAS. The leukocyte migration inhibition was not significantly increased whenStrep. H1, Neisseria subflava, Staphylococcusor fetal human kidney extracts were used as antigens. The IgG antibodies againstStrep. 2AandStrep. H1were significantly raised in sera from patients with exacerbation of RAS. However, the endpoint titers (EPT) did not increase significantly in relation to the exacerbation of RAS. The distribution of EPT againstNeisseria subflava, Staphylococcusand AHOM did not differ significantly when sera from patients with exacerbation of RAS were related to sera from controls. The present investigations support the hypothesis that CMI against streptococcal and AHOM antigens may be involved in the immunopathogenesis o