Sera of 173 individuals living in a malaria endemic region in Upper Volta (Donsé village) were screened for the presence of 14 auto-antibodies by the indirect immunofluorescent and/or passive haemagglutination techniques. At least one auto-antibody (AAb) was detected in sera of 72% (124 out of 173) subjects. No differences in the AAb frequency was observed in the sex or age groups. Conversely, a significant relationship between a high frequency of auto-antibodies, high malaria antibody titres and high IgM levels was observed. Antinuclear antibodies (ANA) (87% of total AAb) and particularly those of speckled pattern of fluorescence were by far the most frequently observed. Smooth muscle antibodies (SMA), heart and gastric parietal cell antibodies and thyroglobulin antibodies were found at a normal frequency. This selective increase in the frequency of one AAb (and not of others) cannot, in our opinion, result from a non-specific polyclonal activation. An alternative hypothesis involving both a specific antigenic and a non-specific mitogenic signal is proposed.