OBJECTIVE To identify the frequency and characteristics of clinical activity with serological quiescence (CASQ) in a large cohort of patients with systemic lupus erythematosus (SLE) followed prospectively at a single center. METHODS Patients followed at the Lupus Clinic between 1991 and 1995 who on at least 3 consecutive visits had clinical activity in the absence of a low complement and elevated DNA binding were identified. Demographics, disease characteristics, and therapy for the CASQ periods, as well as prior and subsequent disease course until April 2002 were analyzed. RESULTS Of 514 patients followed at the Lupus Clinic according to a standard protocol, 62 patients had at least one episode of CASQ lasting a 9.8 +/- 6.4 months. During these periods, patients showed evidence of clinical disease activity with a SLEDAI-2K of 8.9 +/- 5.3. Major organ involvement (central nervous system, renal, vasculitis) occurred in 43 patients. Forty-four patients were treated with prednisone 16.7 +/- 11.4 mg/day, 21 were on immunosuppressive medication and 30 on antimalarials. Of the 58 patients who had followup after their last CASQ defining visit, 9 remained CASQ for 39 +/- 23 months. Of the remaining 49 patients, 23 became inactive, 21 became clinically and serologically active, and 5 were serologically active but clinically quiescent (SACQ). CONCLUSIONS Clinical laboratory correlation in SLE is a heterogeneous relationship. The majority of patients have clinical-serological concordance. The minority have discordance between clinical and serological status, and are either SACQ or CASQ. Therefore, monitoring both clinical and serological features in patients with SLE is important.