There are potentially significant cost benefits through plant simplification if a soluble boron-free lithiated primary water chemistry can be demonstrated to be a viable route for small modular reactor operation. However, the corrosion behavior of the clad material under lithiated conditions remains a concern. High levels of lithium (Li) have been demonstrated to be detrimental to the corrosion behavior of zirconium alloys. Under a thermal gradient, as experienced by the clad in pressurized water reactor operation, this becomes more complex; with increasing oxide thickness, the potential for operation under two-phase (nucleate boiling) conditions increases. The significance of this is twofold: first, the concentration of lithium local to the oxide has been shown to increase as boiling occurs within the thick porous oxide, potentially increasing the Li content beyond the threshold for accelerated corrosion; second, the nucleate boiling can result locally in more aggressive (high lithium) chemistry conditions. This paper presents the results from a test program that has investigated the effect of lithium, temperature, thermal gradient, two-phase flow. and stress on the corrosion behavior of Zircaloy-4 and discusses the results in the context of previous work carried out in this area. The data from this work indicate that in nominal lithium concentrations, under certain combinations of a thermal gradient, two-phase flow, and stress, a significant acceleration in corrosion can be observed. Characterization and modeling of the specimens exposed to a thermal gradient, in comparison to isothermally corroded Zircaloy-4 coupons in a range of Li concentrations, has developed the understanding of the processes occurring during this acceleration.