Olfactory receptor neurons (ORNs) are the only class of neurons that is directly exposed to the environment. Therefore, they need to deal with xenobiotic and potentially cytotoxic substances. Here we show for the first time that ORNs possess transporter systems that expel xenobiotics across the plasma membrane. Using calcein and calcium-indicator dyes as xenobiotics, we demonstrate that ORNs appear to express the multidrug resistance P-glycoprotein (MDR1) and multidrug resistance-associated proteins (MRP). This endows ORNs with the ability to transport a large number of substrates including calcium-indicator dyes and calcein across their plasma membranes. Conversely, blocking P-glycoprotein and MRP increases the net uptake of these dyes.