BACKGROUND: Limited evidence suggests that rizatriptan given before vestibular stimulation reduces motion sickness in persons with migraine-related dizziness. The present study was designed to test whether rizatriptan is also effective in protecting against visually-induced motion sickness and to test whether rizatriptan blocks the augmentation of motion sickness by head pain. MATERIAL AND METHODS: Using randomized double-blind, placebo-controlled methodology, 10 females, 6 with migrainous vertigo (V+) and four without vertigo (V-) received 10 mg rizatriptan or placebo two hours prior to being stimulated by optokinetic stripes. Visual stimulation was coupled with three pain conditions: no pain (N), thermally-induced hand pain (H) and temple pain (T). Motion sickness and subjective discomfort were measured. RESULTS: Motion sickness was less after pre-treatment with rizatriptan for 4 of 10 subjects and more for 5 of 10 subjects. Augmentation of motion sickness by head pain was seen in 6 of 10 subjects; this effect was blunted by rizatriptan in 4 of these 6 subjects. Subjective discomfort was significantly more noticeable in V+ subjects as compared with V- subjects. CONCLUSIONS: These pilot data suggest that rizatriptan does not consistently reduce visually-induced motion sickness in migraineurs. Rizatriptan may diminish motion sickness potentiation by cranial pain.