A high frequency of pulmonary infections has been a well-described feature of systemic lupus erythematosus (SLE). Alveolar macrophages (AM) play a crucial role in pulmonary bacterial defense. We therefore examined the antibacterial activity of AM and generation of superoxide anion in 17 patients with SLE without clinical or radiologic pulmonary changes and in 8 control subjects. Total cell count and cellular viability of AM (trypan blue exclusion) did not differ significantly between patients and control subjects. Antibacterial activity v/s Staphylococcus aureus was significantly decreased in both untreated and corticosteroid-treated patients (respectively, -16.2 +/- 7.4 and -42 +/- 12% compared with the normal value of 51 +/- 12%, p less than 0.001). The defect of antibacterial activity was observed as well v/s S. aureus as v/s Escherichia coli. In contrast, chemiluminescence response of AM before and after stimulation by either phorbol myristate acetate or opsonized zymosan did not differ among control subjects and treated and untreated patients with SLE. We did not find any correlation between disease activity and AM function. Antibacterial activity of normal AM was shown to be significantly reduced by previous incubation with SLE serum compared with normal human serum. Thus, our findings suggest that alteration of antibacterial activity of AM may contribute to the increased susceptibility to lung infections observed in SLE.