Pulmozyme^� recombinant human deoxyribonuclease I (DNase I) is currently used as a therapeutic for cystic fibrosis (CF) (1 ) and may be effective in the treatment of systemic lupus erythematosus (SLE) (2 ,3 ). As described in Chapter 20, degradation of high-molecular-weight DNA following inhalation of DNase I as an aerosol decreases the viscoelasticity of CF sputum and improves lung function. In SLE, antibodies to DNA and DNA/anti-DNA immune complexes have been implicated as the principal causative factor underlying clinical pathogenesis (4 –7 ). Degradation of extracellular DNA or DNA/anti-DNA immune complexes may be of clinical benefit in SLE by two mechanisms. First, hydrolysis of the DNA component of membrane deposited DNA/anti-DNA immune complexes may reduce inflammation in the affected tissues. Second, hydrolysis of DNA and/or DNA/anti-DNA immune complexes in the circulation may elicit a decrease in the production of antibodies to DNA over time by reducing the antigen load (8 ).