Tuberculous meningitis and meningoencephalitis are rare and dangerous complications of infections with mycobacteria-complex. Usually these are complications of systemic florid infection with Mycobacterium (M.) tuberculosis. They are most often seen in immune compromised patients. The confirmation of diagnosis can be elaborate and delayed due to long-term culture requirements for M. tuberculosis. We present a female patient, without history of immunosuppression, who was diagnosed with tuberculous meningoencephalitis using ELISpot to detect immune reactivity against mycobacterial antigens with lymphocytes from cerebrospinal fluid (CSF). ELISpot with CSF derived lymphocytes seems to be an appropriate method to diagnose tuberculous meningitis and meningoencephalitis and to make therapeutic decisions easier and earlier in atypical cases of infection with M. tuberculosis.