The authors report a rare case of a female patient diagnosed with mixed connective tissue disease (MCTD). After a few years in remission, the patient acquired herpes zoster infection followed by a disease flare. Disease activity was accompanied by the development of meningitis. To determine whether the meningitis was caused by the previous herpes virus infection or was aseptic meningitis associated with the activity of MCTD raised important differential diagnostic issues. Repeated laboratory assessments of the patient's sera and cerebrospinal fluid revealed leukocytopenia, high anti-U1 ribonucleoprotein autoantibody level, increased immune complex, and decreased complement concentrations. The administration of corticosteroids resulted in rapid improvements in clinical symptoms and laboratory indicators.