Employing an antibody class capture ELISA, we assessed the significance of enterovirus (EV)-specific serum IgA (EV-IgA) as a marker of EV infection. EV-IgA was detectable in 64% of sera from patients with acute illnesses which may be attributable to EV infection who also had EV-IgM, but also in 30% of sera from patients without evidence of EV infection. High EV-IgA levels were more closely associated with the presence of EV-IgM and were demonstrable in 39% of patients with acute infections who were EV-IgM positive, compared to 3% of those who were EV-IgM negative. Among patients with acute EV infection confirmed by virus isolation, EV-IgA was present in 67% and EV-IgM was present in 83%. As a marker of acute EV infection, EV-IgA is less sensitive and less specific than EV-IgM. EV-IgA responses in patients with chronic cardiac disease paralleled EV-IgM responses in some cases but there was no significant association between these two antibody responses in this group as a whole. High EV-IgA responses were present in 20% of EV-IgM positive and 21% of EV-IgM negative patients, and may persist as a result of an immunoregulatory defect leading to virus or antigen persistence at mucosal surfaces. High EV-IgA levels were also detectable in 33% of EV-IgM positive newly diagnosed insulin-dependent diabetics but in none who were EV-IgM negative, which suggests that most EV infections in these patient were acute rather than persistent.