Indian cobra (Naja naja) venom from different geographical locations varied in its composition and biochemical, pharmacological and immunological properties. Recently it has been shown that the variation in composition of venom from different geographical origin of Indian peninsula is due to the quantitative difference in the same components and also the presence of different biochemical entities with respect to their origin. This disparity in venom composition may be due to several environmental factors. However, very little is known about the systemic effects on vital organs caused by the venom due to regional variation. In the present investigation, the venom samples procured from eastern, western and southern regions were compared for histopathological effects on skeletal muscle and some vital organs (heart, lungs, liver and kidney) in the mouse model. All the three venom samples damaged vital organs such as cardiac muscle, gastrocnemius muscle, liver, lungs and kidneys; however, the extent of damage varied greatly. Eastern venom predominantly damaged cardiac muscle and kidney, western venom injured the liver and the southern venom affected the lung. In addition, the eastern venom caused the recruitment of a flux of inflammatory cells in the skeletal muscle unlike southern and western venom samples. These results suggest the diversity of target-specific toxins in all the three regional venoms. Thus, the study explores the possible variations in the pathological effects of cobra (Naja naja) venom samples on vital organs due to geographical distribution in the Indian subcontinent. It also emphasizes the importance of intra-specific variation of venom samples for the production of efficacious and region-specific therapeutic antivenom. © 2009.