Abstract: An analysis of the profile of antinuclear (ANA) and anti-dsDNA antibodies in sera of SLE patients and related diseases revealed similarities and differences between ANA-immunofluorescence test (IF-ANA), anti-dsDNA using hemagglutination test (HA-dsDNA) and immunofluorescence test (IF-dsDNA) in detecting positive sera. Of 1620 sera examined, 179 (11.0%) were positive for ANA when tested under non-stringent condition (titre 1:10) but only 71 (4.4%) when tested under stringent condition (titre 1:80). Most of the sera from non-SLE patients were negative when tested under the stringent condition. However, Mixed Connective Tissue Disease (MCTD), Discoid Lupus Erythematosus (DLE) and scleroderma exhibited high percentage of ANA positive cases and high titre antibodies. Analysis of anti-dsDNA antibodies in 85 sera from confirmed SLE and 27 non-SLE cases revealed that the different screening method detected antibodies to different autoantigens or different form of the same antigens. The total number of sera detected by HA-dsDNA for SLE and non-SLE sera were 80.7 and 63.0%, respectively. The corresponding values for IF-dsDNA were 73.7 and 0.0%, showing that this test has diagnostic value for SLE. This was supported by the greater reduction in the percentage of positive sera of treated SLE patients when screened with IF-dsDNA method (from 73.7 to 17.9%) as compared to HA-dsDNA (from 80.7 to 71.4%). The implication of this reduction on search for SLE therapeutics was discussed.