Previous studies have shown that neutrophils in the circulation of patients with active systemic lupus erythematosus (SLE) are activated as judged by their increased surface expression of the β2-integrin CD11b/CD18. Since activation of neutrophils leads to altered expression of another adhesion molecule, L-selectin (LS), we examined neutrophils from patients with SLE for changes in the expression of CD11b/CD18 and LS by cytofluorographic analysis of immunofluorescent-labeled cells. Overall there was no difference between surface expression of CD11b/CD18 on neutrophils from SLE patients or controls [mean fluorescence 225 ± 26 vs 225 ± 13 relative fluorescence units (RFU), respectively]. However, as previously reported, neutrophils from patients with more active disease (activity score ≥3, UCH Middlesex activity score) expressed greater CD11b/CD18 than neutrophiIs from controls (319 ± 40 RFU, P < 0.03, n = 9) or from patients with less active disease (193 ± 10 RFU, P < 0.006). Indeed, CD11b/CD18 expression correlated directly with disease activity (r = 0.54, P < 0.02). Stimulation of neutrophils ex vivo with the chemoattractant N-formyl-methionylleucyl-phenylalanine (100 nM) induced up-regulation of CD11b/CD18 in cells from both SLE patients and controls (205 ± 12% vs 239 ± 15% of basal, respectively), but neutrophiIs from the most active patients (score ≥3) increased CD11b/CD18 expression less than controls (175 ± 12% of basal, P < 0.003, n = 9). The magnitude of the stimulated increment in expression of CD11b/CD18 on neutrophils correlated inversely with SLE activity (r = -0.64, P < 0.003, n = 20). Surprisingly, we observed no change in LS expression on neutrophils from SLE patients compared to controls (143 ± 14 vs 141 ± 16 RFU, respectively) even in patients with the highest activity indices (154 ± 21 RFU). In contrast to CD11b/CD18, there was no correlation between LS expression and disease activity (r = 0.12, P = NS). Stimulation of neutrophils reduced the expression of LS similarly in both controls and SLE patients (67 ± 3% vs 58 ± 4% reduction, respectively) and did not correlate with disease activity (r = 0.07, P = NS, n = 20). These results show, for the first time, that changes in CD11b/CD18 expression do not correlate with LS expression on neutrophils from patients with active SLE. Moreover, since C5a and other chemoattractants (over a range of concentrations) stimulated changes of identical magnitude in surface expression of CD11b/CD18 and LS, our data suggest that the exposure of neutrophils to chemoattractants in the circulation of patients with active SLE is not sufficient to account for all of the alterations observed in neutrophil adhesion molecules.