A vacuum-insulated tandem accelerator was used to observe in situ blistering during 2-MeV proton irradiation of metallic samples to a fluence of up to 6.7 × 10 20 cm −2 . Samples consisting of copper of different purity, tantalum and tantalum-copper compounds were placed on the proton beam path and forced to cool. The surface state of the samples was observed using a charge-coupled device camera with a remote microscope. Thermistors, a pyrometer and an infrared camera were applied to measure the temperature of the samples during irradiation. After irradiation, the samples were analyzed on an X-ray diffractometer, laser and electron microscopes. The present study describes the experiment, presents the results obtained and notes their relevance and significance in the development of a lithium target for an accelerator-based neutron source, for use in boron neutron capture therapy of cancer.