The manganese-molybdenum-nickel steels ASTM A533B and A508 are extensively used in the fabrication of reactor pressure vessels and steam generators in light water reactors. These components receive heat treatments during fabrication and in operational service that could lead to a possible degradation of toughness as a result of grain boundary segregation of alloying and impurity elements promoting temper embrittlement. The susceptibilities to temper embrittlement of commercially produced thick section A533B Class 1 and A508 Class 3 steels have been investigated by Charpy impact testing following isothermal heat treatments in the 300 to 600°C temperature range for periods up to 5000 h. In addition, the combined effects of austenite grain size and impurity content have been studied using experimental melts of the 533B/508 Class 3 type alloy composition doped with specific impurities. The lower and upper shelf fracture modes were examined as a function of aging treatment, and samples exhibiting a low temperature intergranular fracture mode were examined using Auger Electron Spectroscopy to determine the amount and types of elements segregated at the grain boundaries. While the commercial materials have been found to exhibit only small increases in the ductile-brittle transition temperature after isothermal aging at 450 to 500°C, large increases are observed for the experimental material with a high phosphorus content. The degree of embrittlement is strongly dependent on austenite grain size, increasing with increasing grain size. These results indicate the need for close control of chemical composition of the steel in inhibiting embrittlement and cracking in the weld coarse-grained, heat-affected zone regions.