To examine the possibility that prostaglandin D synthase in CSF is involved in the brain responses to inflammation, we monitored the enzyme levels before and after administration of a bacterial endotoxin lipopolysaccharide (LPS) or proinflammatory cytokines. After an i.p. injection of LPS, the synthase levels began to rise within 1 day, peaked at 2 days and returned to the basal by 5 days after injection. The enzyme levels increased in a similar manner in response to tumor necrosis factor-alpha or interleukin (IL)-1 beta injected i.v. Centrally administered IL-1 beta had a similar effect. These findings support the hypothesis that PGD synthase in CSF participates in the brain responses to inflammation.