The significance of antibodies against alpha-fodrin compared to antibodies against Ro (SSA) as markers of Sjögren's syndrome has been controversially discussed. We therefore compared the association of alpha-fodrin and Ro antibodies with dry eyes and dry mouth in the general population. In 168 "normal" participants, the prevalence of IgA antibodies against alpha-fodrin was 5% and of IgG antibodies against alpha-fodrin was 3%. IgA antibodies against alpha-fodrin were present in 3 of 4 and IgG antibodies against alpha-fodrin in 2 of 4 participants with the combination of dry eyes and dry mouth (P = 0.0002 and 0.005). Only one participant had antibodies against Ro and had dry eyes but normal saliva production. Antibodies against alpha-fodrin are associated with sicca syndrome and may be valuable diagnostic markers in patients with Sjögren's syndrome lacking Ro antibodies.