The aimed of this study to evaluate the relationship between temperature humidity index (THI) and the changes in physiological responses and hematological aspects of buffaloes and cows under different climatic conditions in Egypt. The data used were collected from six Egyptian Governorates located in three different geographic regions (Lower, Middle and Upper Egypt) during the period from January (2010) to December (2015). Two Governorates from each region were visited to collect the data. In each Governorate, 25 farms randomly selected to represent small, medium and large farms, the measurements were taken from 20 animals divided into (10 buffaloes and 10 cows) in each farm. Each group was divided into two groups (5calves less than year, 5 calves more than year) The environmental conditions were recording air temperature (AT°C) and relative humidity (RH %) to calculate temperature humidity index (THI). The environmental regions based on THI values were classified into four classes (cold, thermal neutral, mild heat stress and moderate heat stress). During farm monitoring, hair temperature (HT°C), skin temperature (ST°C), rectal temperature (RT°C) and respiration rate (RR r/min) of animals were recorded. In addition, blood samples were collected for determining hemoglobin concentration (Hb g/100 ml) and hematocrit (Ht%). The results indicated that, values of HT, ST, RT and RR were slightly higher in cows than in buffaloes among all studied regions.Higher estimates of HT and ST were observed for buffaloes and cows in Lower Egypt (LE) compared with those in Middle Egypt (ME). Both species showed increased HT and ST with elevated temperature in the different climates. Narrow changes in RT among the different seasons and regions were noticed.Values of RR for both species were the highest at LE followed by ME and UE. It was observed that buffaloes have the potentiality to maintain stability of ST within the different climatic conditions. Despite, sensitivity of buffaloes to cold waves was noticeable, the physiological characteristics of buffaloes showed more suitability to hot conditions than cows. Values of Ht% during winter were less than those recorded in other seasons regardless of age category or species. Meanwhile, with subsequent increase in the ambient temperatures Ht % values descended relatively in both species. Value of Ht were noticeably greater in both species of UE compared with LE. or ME. The study revealed the ability of using RR and Ht in particular as predictive measures for animal acclimation based on THI values in each specific region so that livestock holder has the choice to select the appropriate breed for raising to get efficient productivity according to compatibility with his farm location.