INCONEL alloy 600 specimens were irradiated with 2 MeV protons at 300°C to doses of 0.01, 0.1, and 1.0 dpa, at about 6 μm depth, to study the effect of irradiation on the microstructural evolution of this alloy. Two types of specimens were examined; namely, mill-annealed (MA) and solution-annealed and sensitized (SAS). In the mill-annealed specimen, the dislocation structure reached an equilibrium value of 1.2 × 1014 m-2 by 1.0 dpa. M7C3 carbides were the major precipitates and coarsened slightly during irradiation. The void swelling increased sharply with irradiation dose. At 1 dpa, the total swelling was about 0.3%. Previous study showed that the SAS specimens were very susceptible to intergranular stress corrosion cracking (IGSCC) due to the chromium depletion at grain boundaries. Irradiation enhanced the reprecipitation of the M23C6 precipitates in the matrix. Dislocation density increased with increasing irradiation dose due to dislocation loop formation and growth. The chromium depletion was increased by irradiation, which may increase the IGSCC susceptibility of this alloy. It is believed that void swelling and irradiation-assisted stress corrosion cracking will be the major problems for using this alloy for fusion reactor components such as piping.