In this paper, we report two patients with mixed connective tissue disease (MCTD) who developed aseptic meningitis. In both cases, the concentrations of IFN-gamma and IL-6 in cerebrospinal fluid (CSF) were increased. In the first case, with non-steroidal anti-inflammatory drugs (NSAIDs)-induced meningitis, where anti-U1RNP antibodies (Abs) were not detected in CSF, NSAIDs induced both IFN-gamma and IL-6 secretion from peripheral blood mononuclear cells in vitro. In the second case, with disease-associated meningitis, anti-U1RNP Abs were detected also in CSF. Of note, anti-U1RNP Abs appeared to be more concentrated in CSF than in serum and CSF-anti-U1RNP Ab titer was correlated with disease activity. We suggest that IFN-gamma and IL-6 may be involved in both disease-associated and drug-induced aseptic meningitis, whereas CSF-anti-U1RNP Abs is detected only in a patient with MCTD-associated aseptic meningitis.