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Objectives: This study sought to create a model for testing topical treatment of jellyfish stings. It sought to determine which treatments 1) stimulate/inhibit nematocyst discharge; 2) decrease pain; and 3) decrease skin inflammation; it also sought to discover whether there is a clinical correlation between stimulated nematocyst discharge observed in vitro to the pain and erythema experienced by humans stung by a particular species of jellyfish, C chinensis., Methods: Chrysaora chinensis stung 96 human subjects, who were then treated with isopropyl alcohol, hot water, acetic acid, papain meat tenderizer, lidocaine, or sodium bicarbonate. Pain and erythema were measured. In a separate experiment, nematocysts were examined microscopically after exposure to the same topical treatments used in the human experiment., Results: Forearms treated with papain showed decreased mean pain over the first 30 minutes after being stung, relative to placebo, although only by a small amount. The other topical treatments tested did not reach statistical significance. Sodium bicarbonate may reduce erythema after 30 minutes of treatment; sodium bicarbonate and papain may reduce erythema at 60 minutes. The other topical treatments tested did not reach statistical significance. Nematocyst discharge in vitro occurred when tentacles of C chinensis were exposed to acetic acid or isopropyl alcohol. Sodium bicarbonate, papain, heated water, and lidocaine did not induce nematocyst discharge., Conclusions: Papain-containing meat tenderizer used as a topical treatment for C chinensis stings may decrease pain. Although there is published experimental support for the concept that in vitro nematocyst discharge correlates with in vivo human pain perception, no definitive randomized controlled trial, including ours, has yet provided incontrovertible evidence of this assertion. Despite this study's limitations, it presents a viable basis for future human studies looking at the efficacy of topical treatments for jellyfish stings., (Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)