To evaluate cervicovaginal cytology in adolescents with juvenile systemic lupus erythematosus (JSLE) and to compare them to controls. Fifty-two female adolescents with JSLE (ACR criteria) were compared to 52 age-matched healthy controls. All Pap smears were evaluated by the same cytopathologist blinded to gynecology examination (Bethesda 2001). The mean age of JSLE patients and controls were similar (16.17 +/- 1.94 versus 16.13 +/- 2.16 years, P = 0.92). The cervicovaginal cytology was found to be similar in both groups, although sexual intercourses in the last month were less frequent in JSLE than controls (23% versus 59.6%, P = 0.0003). Only one patient (2%) with JSLE versus two controls (4%) had cervical dysplasia (LGSIL) and human papilomavirus (P = 1.0). Candida spp vaginitis was observed in seven JSLE (14%) versus none in controls (P = 0.012) and was associated with immunosuppressive drugs (P = 0.01) and high dose of prednisone (P = 0.002). Of interest, inflammatory cervicovaginal cytology was observed in 21 (60%) of patients with SLEDAI > or = 4 and only four (23%) of those with SLEDAI < 4 (P = 0.001). Likewise, a higher frequency of inflammatory changes was also observed in virgin JSLE (57% versus 8%, P = 0.005). Our findings supports the notion that female genital tract may be a potential target organ in SLE since cervical inflammation is associated to disease activity independently of sexual activity.