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The growth–differentiation balance (GDB) hypothesis (as elaborated by Herms and Mattson) provides a framework for examining the impact of a resource gradient on the constant tradeoff between growth and differentiation in cells and tissues of plants, in particular with the consequences for plant defense. The GDB hypothesis, which is the most mature of the hypotheses of plant defensive levels, has not been tested directly. Examination of the requirements for a rigorous test indicates that, like the other hypotheses of plant defense, it cannot be tested directly. Furthermore, rigorously testing the primary derivative hypotheses, while possible, would require considerable methodological effort, on a scale not previously attempted for tests of plant defense, which is likely to discourage researchers, and understandably so, even though the GDB hypothesis warrants methodical investigation due to its potential explanatory power. Although farther removed from the abstract model (i.e. the GDB framework), other derivative hypotheses can be tested, but doing so will require thoughtful consideration and acknowledgement of that. Study of a few carefully chosen systems (i.e. plant species) may provide considerable insight and potentially useful refinement of the GDB framework.