We examined development time, survival, adult body weights, and metabolic pools of protein, triglycerides and glycogen in three Drosophila species reared on three isocaloric diets differing in their relative ratios of sugar to protein. Drosophila melanogaster, a fruit breeder, survived and developed well on all three diets. But two other species, the cactophilic D. arizonae and D. mojavensis, normally accustomed to low carbohydrate resources in nature, were significantly impaired by diets higher in sugar. As expected, based upon their natural history, D. arizonae was less affected than D. mojavensis. These species, whose genomes are sequenced and have many homologues with human metabolism genes, provide an inexpensive and tractable model system to study human metabolic diseases related to excess dietary sugar.