We prospectively evaluated 24 patients with systemic lupus erythematosus for clinical, histologic, and serologic evidence of sicca syndrome. Abnormalties suggestive of sicca syndrome in patients with systemic lupus were identified by parotid scan (58%), questionnaire (54%), labial biopsy (50%), Schirmer's test (21%), and parotid flow rate (13%). An increased frequency of autoantibodies to gamma globulin and cellular antigen SS-A was detected in lupus patients with histologic changes on labial biopsy. The serologic findings are similar to those of patients with sicca syndrome alone with the exception of the reduced incidence of anti-SS-B in patients with systemic lupus.