Background.-The vasoactive peptide, calcitonin gene-related peptide (CGRP), is released from primary afferent neurons in the trigemino-vascular circulation during migraine headache. CGRP at physiological concentrations and possibly via stimulation of its selective receptors on T-cells, triggers the secretion of cytokines. Cytokines play an important role in several physiological and pathological settings such as immunology, inflammation, and pain. Objective.-To investigate plasma levels of pro- and anti-inflammatory cytokines in migraineurs and healthy controls. Methods.-We studied 25 migraine patients, during and outside attacks, and 18 healthy control subjects measuring plasma levels of IL-6, IL-10, tumor necrosis factor alpha (TNF alpha), IL-4, IL-1 beta, and IL-2 using ELISA. Results.-Circulating levels of IL-10, TNF alpha, and IL-1 beta during attacks were significantly higher in comparison to their levels outside attacks (P =.0003, P = .03, and P = .05, respectively). IL-10 and TNF serum levels were higher in patients studied soon after headache onset and lower over time (P = .004 and P = .05). Conclusion.-Our results suggest that TNF alpha, IL-1 beta, and IL-10 may be involved in the pathogenesis of migraine attacks.