We studied interferon-gamma (IFN-gamma), alpha-tumor necrosis factor (alpha-TNF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in the cerebrospinal fluid and serum of 18 patients with multiple sclerosis (MS) and 10 subjects with other neurological diseases (OND). We also studied the cerebrospinal-fluid CD 69 expression, and T cells with T cell receptor (TcR) gamma/delta+. We found an increase of IFN-gamma (14.0 +/- 3.5 U/ml) and GM-CSF (8.0 +/- 3.4 pg/ml) levels in the cerebrospinal fluid of MS patients compared to the OND group (p < 0.005 and p < 0.01, respectively). The frequency of detectable cerebrospinal-fluid and serum alpha-TNF was similar in patients with MS and with OND. The cerebrospinal-fluid CD69 expression in lymphocytes was significantly higher in MS patients (15.0 +/- 9.9%) than in the control group (3.7 +/- 6.2%; p < 0.005). Comparable serum levels of IFN-gamma and GM-CSF were detected in patients with MS and in OND subjects. No significant difference in the incidence of TcR gamma/delta+ in the cerebrospinal fluid was found between the two groups. These results indicate an activation of T lymphocytes and macrophages in patients with MS. Our data do not suggest a role for an increased incidence of TcR gamma/delta+. However, we cannot rule out the possibility that these T cells could be present at the plaque site of MS patients.