We have investigated the permeability of the human red blood cell to four di-hydroxy alcohols, 1,2PD (1,2 propanediol), 1,3PD (1.3 propanediol), 1,4BD (1,4 butanediol), and 2,3BD (2,3 butanediol), and to water by using a recently developed ESR stopped-flow method which is free from artifacts found in light scattering methods. Numerical solutions of the Kedem-Katchalsky equations fit to experimental data yielded the following permeability coefficients: P1,2PD = 3.17 x 10(-5) cm sec-1, P1,3PD = 1.75 x 10(-5) cm sec-1, P1,4BD = 2.05 x 10(-5) cm sec-1, P2,3BD = 7.32 x 10(-5) cm sec-1. Reflection coefficients (sigma) were evaluated by comparing data fit with assumed values of sigma = 0.6, 0.8 and 1.0. In all four cases the best fit was obtained with sigma = 1.0. Treatment of cells with PCMBS (para-chloro mercuri-benzene-sulfonate) was followed by a large (> 10-fold) decrease in water permeability with virtually no change in alcohol permeability. We conclude that these alcohols do not permeate the water channels to any significant extent, and discuss some of the problems in light scattering measurements of reflection coefficients that could lead to erroneous values for sigma.