Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] flesh color is controlled by several genes to produce red, canary yellow, salmon yellow, and orange. Our objective was to study the interaction of three gene loci with two or three alleles at each C (canary yellow vs. red), y (salmon yellow vs. red), yo (orange), and i (inhibitory to C permitting Y to produce red flesh color). Five crosses were used to study gene action: `Yellow Baby' × `Sweet Princess', `Yellow Baby' × `Tendersweet Orange Flesh', `Yellow Baby' × `Golden Honey', `Yellow Doll' × `Tendersweet Orange Flesh', and `Yellow Doll' × `Golden Honey'. Based on the performance of six generations (PA, PB, F1, F2, BC1A, and BC1B), the parents had the following genotypes: `Yellow Baby' = CCYYII, `Yellow Doll' = CCYYII, `Sweet Princess' = ccYY ii, `Tendersweet Orange Flesh' = ccyoyoII, and `Golden Honey' = ccyyII. Segregation of flesh colors in the progeny of the five families demonstrated that there was a multiple allelic series at the y locus, where YY (red) was dominant to yo yo (orange) and yy (yellow). Also, yoyo was dominant to yy. In conclusion, epistasis is involved in genes for the major flesh colors in watermelon, with ii inhibitory to CC (Canary), resulting in red flesh, and CC in the absence of ii epistatic to YY, producing canary flesh.