Technical Abstract: Muskmelon (Cucumis melo L.) fruit matrix is unique among plant foods in being able to provide a protective medium in which the antioxidant activity of the enzyme superoxide dismutase (SOD) is preserved during the digestive process, and therefore, being able to elicit in vivo pharmacological effects of this enzyme. However, little is known about the variability of SOD activity in the melon germplasm and the potential of this species as a food-based source of SOD. In this study, SOD activities of diverse advanced breeding lines and commercial melon cultivars grown in two different soil types – clay or sandy loam – were investigated. Specific and total SOD activities varied significantly among the genotypes (P less than or equal to 0.001), compared to soil type (P less than or equal to 0.055). Netted (cantaloupe) genotypes generally had the lowest SOD activities compared to the green- and orange-fleshed honey dew types. Casaba type fruit had average SOD activities that were approximately 1.6-fold greater than those of honey dew types, and approximately 9.0-fold greater than those of cantaloupe types. These data indicate there is a useful genetic diversity among commercial melon varieties and in exotic genotypes that could be used to develop C. melo pharmacologically as an SOD treatment.