Cellular immunocompetence of cerebrospinal fluid lymphocytes was investigated in several neurologic diseases. Microtechniques were developed to enable determination of E-rosetting capacity and phytohemagglutinin responsiveness of scant numbers of cells present in the cerebrospinal fluid specimens studied. Although most individuals had phytohemagglutinin-responsive cells in their CSF, reactivity was somewhat less than that found simultaneously in their blood. Three of eight patients had comparable percentages of E rosettes in their blood and CSF. In the remainder, the values differed significantly. Although preliminary, these results illustrate a new approach to immunologic characterization of CSF lymphocytes in diseases.