B cells lacking RP105 molecule, a member of the Toll-like receptor family, were increased in the peripheral blood of 2 patients with antinuclear antibody (ANA) negative systemic lupus erythematosus (SLE). The increased proportion of RP105-lacking B cells was associated with disease activity in patients with ANA-negative SLE. When there are no significant serological markers for SLE, analysis of expression of RP105 may be helpful in evaluation of activity in ANA-negative SLE. We describe a new approach, using phenotyping of B cells, to evaluate activity of ANA-negative SLE.