Serotonin is one of the chemical mediators associated with nerve root inflammation and sciatic symptoms in lumbar disc herniation. The efficacy of serotonin 5-HT(2A) receptor blocker was examined in 44 patients with symptomatic lumbar disc herniation. A selective 5-HT(2A) receptor blocker (sarpogrelate hydroxychloride) was administered orally at a dose of 300 mg per day for 2 weeks. Visual analog scales of low back pain, sciatic pain, and numbness were significantly improved after the administration of the serotonin 5-HT(2A) receptor blocker. Clinical results were good (> 50% pain relief) in 23 patients, fair (25%-50% pain relief) in five patients, and poor (< 25% of pain relief) in 16 patients. Nineteen patients eventually required surgery because of muscle weakness or cauda equina symptoms. The effect of 5-HT(2A) blocker was good in 64% of patients who had uncontained disc herniation, whereas all patients with contained disc herniation had fair or poor results. Patients with uncontained disc herniation responded more favorably to the 5-HT(2A) blocker treatment than patients with contained disc herniation. A 5-HT(2A) blocker has the potential to block the cascade of acute nerve root inflammation and to alleviate symptoms in lumbar disc herniation.