Several studies of the urea transporter UT-B expressed in Xenopus oocytes and in genetically modified red blood cells (RBC) have concluded that UT-B also transports water. In the present study, we use unmodified RBC to test that conclusion. We find that the permeability of urea, Pu (cm/s), has a 10-fold donor variation, while the diffusional water permeability, Pd (cm/s), remains unchanged. Additionally, we observe that phloretin inhibits Pu but not Pd, and that the time course of maximum p-chloromercuribenzosulfonate inhibition of Pu and Pd differs-Pu inhibition takes <2 min, whereas Pd inhibition requires ≥1 h of incubation. The findings in the present study are in line with a previous comparative study using unmodified RBC from four animals and a solvent drag study using human RBC, and they lead us to reject the conclusion that the UT-B transporter represents a common pathway for both solutes.