The experimental investigation of a prototypical set-up simulating a loss of flow accident in a helium-cooled breeding blanket first wall mock-up under typical heat load conditions is presented. The experimental campaign reproduces the expected DEMO thermal-hydraulics conditions during normal and off-normal situations and aims at providing some insight into the fast transients associated with the loss of flow in the blanket first wall. The experimental set-up and the definition of the experimental matrix are discussed, including pre-test analysis performed in support of these activities. The major experimental results are discussed, and a procedure of using the acquired data for validating and calibrating the RELAP-3D model of the mock-up is introduced. All these activities contributed to the creation of a relevant theoretical and practical experience that can be used in further studies concerning incidental transients in real-plant scenarios in the framework of DEMO plant fusion safety activities.