This research investigates sessile drop interfacial reactions between two refractory materials (high-chromia and alumina) and two synthetic slags (coal and petcoke). Pulverized slag samples were placed at specific microstructure locations on refractory substrates and heated to 1500 °C at log(Po 2) = -9, using a high-speed heating chamber. Cross-sections of the slag/refractory interface indicated unique slag penetration into preferred areas of the refractory and grain dissolution into the slag through a de-bonding mechanism. Initially, the slag attacked both grain boundaries and fine microstructure areas, freeing alumina grains into the slag. Crystalline VO x formation in the petcoke slag was found to alter the overall liquid composition. Chemical spallation of Cr-containing crystal layer facilitated degradation of the refractory.