In this study, a constitutive analysis of the flow responses of Ti-6Al-4V under various strain rates (epsilon)over dot was conducted by separately quantifying the hardening and softening effects of microstructure, interstitial solute and deformation heating on the total stress. For this purpose, a series of compression tests on an extra-low interstitial grade alloy with equiaxed, lamellar, or bimodal microstructures was performed at 10(-3) <= (epsilon) over dot <= 10 s(-1) until the metal fractured, and the results were compared to those of the commercial grade alloy. The thermal stress sigma* increased with an increasing interstitial solute concentration; the athermal stress increased in the order of equiaxed, lamellar, and bimodal microstructures. Load-unload-reload tests revealed that the flow softening at a relatively high (epsilon) over dot was likely caused by deformation heating rather than by microstructure change; thus flow softening was attributed to a decrease in sigma*. Finally, a mechanical threshold stress model was extended to capture those observations; the modified model can provide a reasonable prediction of flow stress in Ti-6Al-4V with different microstructures and interstitial solute concentrations.