Free kappa and lambda light chains were assayed by particle-counting immunoassay in cerebrospinal fluid (CSF) from patients with various neurological disorders. Detection limits were 25 and 50 ng/ml, respectively. Values of free kappa chain were higher than 50 ng/ml (upper reference limit) in 155 of 191 (81%) multiple sclerosis (MS) patients, in 100 of 168 (60%) patients with central nervous system (CNS) infections but in 41 of 217 (19%) patients with other neurological disorders. Free kappa chains were also assayed in 273 matched sera. The mean concentration in the control group (1.58 micrograms/ml; SD: 0.41) did not differ significantly from those in MS sera (1.63 micrograms/ml; SD: 0.43). The free kappa chain index was increased in 86% of MS patients and in 40% of patients with CNS infections. Regarding free lambda chains, CSF values were higher than 240 ng/ml (upper reference limit) in most neurological disorders (50-100%). However, the use of a lambda chain index increased the specificity of the assay as this index was higher than the upper reference value in 86% of MS patients and in only 23% of patients with infectious diseases. In MS, high levels of free kappa and lambda indices correlated significantly (P less than 0.01) with either the presence of oligoclonal bands or a high IgG index. Local synthesis of free light chains is an additional marker of an ongoing immune response within the CNS, especially in MS.