Sera from 32 subjects with Plasmodium falciparum parasitaemia were screened for the presence of antibodies to native-double stranded (ds) DNA and to heat-denaturated-single stranded (ss) DNA by a Farr DNA binding radioimmunoassay. In addition anti-dsDNA antibodies were also studied by indirect immunofluorescence using Crithidia luciliae and rat liver sections as substrates. Immunoglobulin (G, A, M) levels and plasmodial antibodies titres (PA) were concomitantly evaluated. The anti-ssDNA activity was higher in malarious individuals with high IgM levels than in normal or malarious individuals with normal IgM levels. This activity was higher during the acute stage of infection than after recovery. A positive and significant relationship was found between the anti-ssDNA activity and the IgM levels but not with IgG, IgA or PA titres. Speckled antinuclear antibodies (ANA) were also observed in sera from 43.8% of the individuals and the mean ssDNA activity was higher in these ANA positive patients. Conversely anti-dsDNA antibodies could not be detected by any of the tests performed. This preferential production of anti-ssDNA Ab and not anti-dsDNA Ab is additional evidence that the autoantibodies observed in malaria infection are not a consequence of a generalized and non-specific polyclonal activation.