The main objective of this study is to determine the relationship between the activity of DNase1 and the clinical and immunological features in patients with systemic lupus erythematosus (SLE). A total of 66 patients (8 men and 58 women) diagnosed with SLE according to the American College of Rheumatology (ACR) SLE classification criteria were included in the study. Sixty-two sera from healthy blood donors were also included as controls. Epidemiological, clinical, immunological and therapeutical features for each patient were obtained. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). DNase1 activity was determined by using a radial enzyme diffusion method. Statistical analysis was performed using SPSS 12.0 software, with significant P value <0.05. Dnase1 activity was lower in patients with SLE than in the control group: 13.69 +/- 8.52 mug/mL vs 24.75 +/- 12.32 mug/mL, respectively (P < 0.005). No statistical relationship was found between DNase1 activity and disease evolution time, hypertension, presence of absolute or relative proteinuria, SLEDAI, new clinical manifestations, anti-Ro antibodies, anti-La antibodies, anti-RNP antibodies, anti-DNA antibodies, anti-cardiolipin antibodies, lupus anticoagulant, or with the treatment pattern received by the patients. Although important differences in DNase1 activity were found between patients with or without anti-Sm antibodies, they did not reach statistical significance. DNase1 activity was significantly lower in patients with SLE. Nevertheless, we did not find further relationships with any other of the epidemiological, clinical, immunological or therapeutical variables considered.