Laboratory findings for cerebrospinal fluid (CSF) specimens were correlated with clinical presentations and histories in 55 cases of encephalitis or meningitis due to herpes simplex virus (HSV), as determined by polymerase chain reaction (PCR)-based detection of HSV DNA. Sixteen patients (29%) had HSV encephalitis (HSVE), 3 had mild or "atypical" meningoencephalitis, 34 (64%) had HSV meningitis (HSVM), and 1 had disseminated neonatal HSV infection. CSF findings included elevated leukocyte counts and/or elevated CSF protein levels in all HIV DNA-positive specimens. CSF leukocyte and protein abnormalities were more pronounced in cases of HSVM than they are in cases of HSVE. Patients with HSVE who had only mild CSF abnormalities also had minimal numbers of erythrocytes in the CSF. Patients with HSVM were younger than were patients with HSVE and were predominantly female. Eleven patients with HSVM reported having prior episodes, and 5 reported a history of recurrent headaches. These findings suggest that milder forms of HSV infection of the central nervous system may be identified by PCR for HSV. Prescreening of CSF specimens for the presence of leukocytes or elevated protein level may improve test utilization.