We analyzed CSF from patients with multiple sclerosis, patients with other neurologic diseases, and healthy controls for the presence of prostaglandin (PG) E2, F2 alpha, D2, I, A, and leukotriene (LT) C4. Control CSF had little measurable PGs or LTs. CSF eicosanoids from patients with progressive MS were increased. We found PGD2 only in MS CSF. CSF monocytes from patients in active disease produced significantly increased PGD, PGE, and LTC4 than paired peripheral blood monocytes and monocytes from healthy controls. We saw no significant difference in LTC4 production between MS and control peripheral blood monocytes.