Overall climate sensitivity to CO2 doubling in a general circulation model results from a complex system of parameterizations in combination with the underlying model structure. We refer to this as the model's major hypothesis , and we assume it to be testable. We explain four criteria that a valid test should meet: measurability, specificity, independence, and uniqueness. We argue that temperature change in the tropical 200‐ to 300‐hPa layer meets these criteria. Comparing modeled to observed trends over the past 60 years using a persistence‐robust variance estimator shows that all models warm more rapidly than observations and in the majority of individual cases the discrepancy is statistically significant. We argue that this provides informative evidence against the major hypothesis in most current climate models.