The local production of tumour necrosis factor-alpha (TNFalpha) was evaluated in the cerebrospinal fluid (CSF) from ten patients with tuberculous meningitis (TBM). The degree of intrathecal immune activation was also studied by assessing the CSF levels of beta(2)-microglobulin (beta(2)-M) and adenosine deaminase activity (ADA). Results indicate that elevated CSF concentrations of TNFalpha, beta(2)-M and ADA were found in all TBM patients. Moreover, TNFalpha is produced and selectively concentrated for a long period of time, while beta(2)-M and ADA values progressively decline during the course of TBM. Our findings suggest that in TBM patients, after an early activation of immune cells, there is an enhanced and continuous production of TNFalpha at the site of infection.