Despite the enormous societal and personal burden of fibromyalgia (FM), effective treatment for this condition remains suboptimal. Only one-third of patients in clinical trials derive at least some benefit from currently FDA-approved drugs for FM. Poor treatment outcomes may be accounted for by the absence of drugs that target other aspects of the pathophysiology of FM. Increased number of skin mast cell, a powerful inflammatory cell, has been noted in FM skin biopsies. Mast cells mediators (e.g., chemokines) maybe a potential source of increased peripheral stimuli reaching the central nervous system that induce and/or maintain central sensitization. Interestingly, blood levels of chemokines (i.e., IL-8, MCP-1 and eotaxin) have been reported to be elevated in patients with FM. Despite growing evidence of the immunologic basis of FM however, drug trials have largely focused on centrally-acting agents that influence the ascending (e.g., pregabalin) or the descending (e.g., serotonin-norepinephrine reuptake inhibitors) pain pathways. Perhaps adjunctive therapies directed against inflammatory mediators or towards mast cells may improve the dismal treatment outcomes in FM. Therefore, we propose to conduct a randomized clinical trial using ketotifen (mast cell stabilizer) for FM, and to obtain preliminary estimates of treatment effects for use in designing a larger trial. After a one week placebo run-in phase, 38 FM patients will be randomized to receive ketotifen or placebo for 10 weeks. Outcome assessments at baseline (week 0) and week 11 will include the following: weekly average pain severity, chemokine levels (i.e., IL-8, MCP-1 and eotaxin) and pressure pain threshold. The proposed research is innovative because it will be the first to investigate the effects of an immune-based therapy on FM-related pain, and also the first to evaluate chemokines as biomarkers of disease severity.