Inflammatory conditions of the central nervous system (CNS) are often marked by an increase in lymphocyte number in the cerebrospinal fluid (CSF). In order to determine if changes in CSF cell numbers can alter T-lymphocyte subset composition in CSF or in blood, cell surface markers were evaluated in 25 CSF and paired blood samples from a variety of neurologically affected patients. T-cell subset levels in peripheral blood did not reflect subset levels in paired CSF samples. However, CSF samples with elevated cell numbers (greater than 3 cells/mm3) had significantly increased levels of Leu-3+ T-cells (P less than 0.001), but not Leu-2+ T-cells relative to CSF samples with low cell counts. These data suggest a selective increase in the Leu-3+ T-lymphocyte subset in CSFs with increased cellularity in patients with acute neurologic signs.