We have developed an ELISA to measure murine autoantibodies to the collagenous region (CLR) of C1q, using the whole human C1q molecule as the solid‐phase ligand, in the presence of 1 m NaCl. The assay was validated by testing positive sera from 20 mice using purified mouse C1q, and from 10 mice using purified human C1q‐CLR, as the solid‐phase ligands. There were highly significant correlations between results obtained with human C1q (whole molecule) and: (i) mouse C1q (r_Sp = 0.73, P < 0.001), and (ii) human C1q‐CLR alone (r_Sp = 0.86, P = 0.001). Antibodies to C1q were measured in 53 MRL/lpr, 17 BXSB and 25 NZB/W lupus‐prone mice. Median (range) anti‐C1q (CLR) antibody levels in MRL/lpr, BXSB, and NZB/W autoimmune mice aged 3 months were 22 (16–66), 21 (17–39) and 19 (15–27) EU, respectively. The median anti‐C1q antibody level in MRL/lpr mice aged 5 months was 76 (35–142) EU, significantly higher than that at 3 months (U = 558, P < 0.0005). Median anti‐C1q antibody level in NZB/W mice at 8 months was 37 (13–74) EU and in BXSB mice at 11 months was 62 (31–231) EU, significantly higher than corresponding values at 3 months (U = 326, and U = 4, P < 0.001, respectively). This is the first demonstration of anti‐C1q (CLR) antibodies in NZB/W and BXSB mice. The pathologic significance and the potential utility of these antibodies for monitoring disease in lupus‐prone mice are under evaluation.