The absorption out of antinuclear antibody (ANA) from sera of highly ANA-positive C57BL/6 mice was obtained by different cellular and noncellular factors. A single injection of DNA, liver nuclei, thymocytes, or repeated injections of a soluble material produced by normal mouse splenocytes with (SIRS+) or without (SIRS−) previous stimulation with Con A into ANA-positive mice induced a transient decrease in ANA level, reaching minimal levels at about 14 days after treatment. A similar elimination of ANA was also achieved by in vitro treatment of positive ANA sera from mice or SLE patients with thymocytes, SIRS (+), or SIRS (−). The absorbed ANA could be released by further treatment with DNase, thus indicating that the absorption-out phenomenon involved immune-complex formation.