sHLA are soluble class I antigens produced by lymphocytes on early activation. We have studied the sHLA index IH = (CSF sHLA/serum sHLA)/(CSF albumin/serum albumin), which reflects the intrathecal synthesis (ITS) of sHLA in 23 intravenous drug abusers with central nervous system (CNS) HIV infection. Their mean IH value was increased and directly correlated with ITS of IgG against HIV when the total group of patients was studied; however, 8 of them, who suffered from concomitant tuberculous meningitis, had a decreased IH. The relationship between this index, blood-brain barrier (BBB) function, and HIV and tuberculous infection was also studied. We consider IH an index of lymphocyte activation within the CNS. Its decrease in patients with CNS HIV infection may reflect the presence of a meningeal opportunistic infection due to Mycobacterium tuberculosis.