P-glycoproteins (P-gp) are transmemebrane glycoproteins associated with the multidrug resistance (MDR) phenotype. The P-gp functions as an ATP-dependent transporter of a diverse xenobiotic and pharmologic compounds to effectively lower their intracellular concentration. As such, P-gp is believed to be a significant component of the blood-brainbarrier (BBB) in mammals. We carried out a study to investigate whether P-gp could be detected in normal and in horses afflicted with equine motor neuron disease (EMND). Fresh samples were harvested at necropsy from seven horses diagnosed with EMND and three control horses and immediately frozen in liquid nitrogen until processing. The samples included tissues from the adrenal gland, kidney, liver, small intestine, brain stem, and spinal cord. These tissues were evaluated for P-gp immunoreactivity using monoclonal antibody (C494). Normal and EMND afflicted horses expressed the P-gp at similar levels in the adrenal cortex (100%), the renal proximal tubules (57%), and small intestinal enterocytes (60%).There was no significant difference in the P-gp expression rates between the EMND affected horses and controls. None of the liver and central nervous tissue samples exhibited any P-gp staining. The overall results of our investigation indicate that abundant P-gp expression can be detected in some of the equine tissues using the immunohistochemical methods. The ability to detect P-gp in equine tissues might help in determining its specific role in the etiology of EMND.