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Background: Allergic reactions to fish are a common cause of food allergy in many areas of the world where fish is a major source of protein. Although different species of fish may be consumed, possible cross-reactivity has received limited investigation. Objective: The aim of this study was to assess potential cross-reactivity to different species of fish species using double-blind, placebo-controlled food challenges (DBPCFC) in fish-allergic adults and to compare skin test and RAST reactivity with the challenge response. Methods: Nine skin prick test tired/or RAST-positive adult individuals with histories of all immediate-type reaction following fish ingestion were challenged with different fish species using double-blind, placebo-controlled food challenge. Results: Of a total of 19 double-blind, placebo-controlled fish challenges performed, 14 challenges (74%) resulted in the induction of objective signs that were consistent with an lgEmediated response. The most common sign observed was emesis (37%); the most prevalent subjective symptoms reported were compatible with the oral allergy syndrome (84%)). Three subjects reacted to at least three fish species and one subject reacted to two fish species tested. In regard to the positive challenges, predictive accuracy of skin prick test and RAST was 84% and 78%, respectively. Conclusion: Our results indicate that clinically relevant cross-reactivity among various species of fish may exist. Advising fish-allergic subjects to avoid all fish species should be emphasized until a species can be proven safe to eat by provocative challenge.