Early diagnosis of the central nervous system (CNS) infections is a precondition of their successful treatment. However, the essential standard examination of the cerebrospinal fluid (CSF) is sometimes neither specific enough to define their basic nature, nor sufficient to differentiate them from processes of non-infectious origin. Supposing that the released surface molecules of activated immunocompetent cells could better define the character of inflammatory reaction, the levels of soluble CD4 antigens (sCD4) were determined with enzyme-immunosorbent test in the CSF of the patients with various CNS diseases. In contrast to cerebrovascular insults toxic-metabolic, and other conditions in control group, detectable sCD4 concentrations in acute encephalitis (24 ± 11U/ml) were verified at the beginning of the disease, being also present in cytologically diagnosed normal CSF findings. They were significantly higher (p<0.05) compared to acute serous meningitis (13.5 ± 8 U/ml), while in purulent meningitis they were measurable only after the disease progression - in correlation with the disturbed brain system function. The obtained results suggested the significance of CD4 antigen levels in CSF as a sensitive and specific marker of lymphocytic infiltration of the brain parenchyma, the measurement of which could contribute to early identification of the CNS infections better understanding of their pathogenesis, and the assessment of the actual level of the destruction of neurons.