During severe hydrotreating, several chemical changes take place in the oil, which may lead to the formation of unstable products in which asphaltenic precipitates are released either in the downstream equipment or during storage of products. In the ongoing development of new hydrotreating processes and catalysts it is important to take steps to minimize this tendency. Hence, the chemistry and stability of two oils of Middle East origin have been followed as a function of reactor temperature. The stability was measured using flocculation titrations, and the stability parameters were correlated with chemical changes of both the oil and the asphaltenes. The changes in asphaltene chemistry were followed by, for example, elemental analyses, size exclusion chromatography, and vapor pressure osmometry. By combining the stability measurements and the chemical characterization, the mechanisms responsible for the formation of the asphaltenic material can be followed. At high reaction temperature, the products become unstable due to an increased degree of cracking that changes the solubility parameters of both the asphaltenes and the oil.