Herpes simplex virus (HSV) is known to establish latency in human trigeminal ganglia. It has been speculated that the virus might also be present in latent fashion in normal human brain, where it might be responsible for conditions such as herpes simplex encephalitis, and less plausibly as a cause for multiple sclerosis or Alzheimer's disease. To test the possibility that HSV exists in normal human brain, we utilized the polymerase chain reaction to assess the frequency and distribution of HSV genomes in the nervous system tissues of patients dying of nonneurological causes. Nine samples were obtained in a systematic fashion from olfactory bulb, gyrus rectus, hippocampus amygdala, calcarine cortex, pons, medulla, cerebellum, and trigeminal ganglia from each of 40 individuals dying of nonneurological disease. HSV genomes were sought in each sample using primers from four regions of the HSV genome. The primers were capable of detecting HSV genomic sequences from as little as 10 fg of DNA. HSV genomic sequences were identified in 26 (65%) of 40 samples of trigeminal ganglia. From 30 patients seropositive to HSV, sequences were amplified from 23 (77%). HSV genomic sequences could be amplified and detected in 14 (35%) of 40 brains. The positive areas included medulla, olfactory bulbs, pons, gyrus rectus, amygdala, and hippocampus. The study has confirmed the previous demonstration of latent HSV in trigeminal ganglia in normal humans. The frequency of latent HSV in trigeminal ganglia is in general agreement with results obtained by explanation of ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)