Various catalytic antibodies or abzymes have been detected in the sera of patients with several autoimmune pathologies, and recently we have shown that RNase activity is associated with IgGs and IgMs from the sera of patients with systemic lupus erythematosus (SLE) but not with those from the sera of normal humans. Here we present for the first time convincing evidence showing that highly purified SLE IgG, its F(ab) fragments and separated L-chains catalyze RNA hydrolysis. These IgGs hydrolyze RNA about one to three orders of magnitude faster than DNA. The enzymatic properties of the RNase activity of these polyclonal IgGs distinguish them from other known human RNases. Their specific activity in hydrolysis of ribooligoadenylates is 2-100-fold higher than that of RNase A and human serum RNases, and they are markedly more thermolabile. In addition, their specific activities with different oligonucleotide substrates, optimal pHs, apparent K(m) values for substrates, and substrate specificities varied very much for different patients. These findings show that a pool of polyclonal RNA-hydrolyzing IgG, which may be relatively small or extremely large, is generated by the immune system of SLE patients.