The effects of four phenol derivatives on the Ca2+ and K+ permeability of human red cells were studied at 0 degree C using 45Ca2+ and 86Rb+. Pentachlorophenol (PCP) and 2,4,6-trinitrophenol (TNP), which are mainly ionized at physiological pH, produced a marked influx of Ca2+ that increased with increasing pH. The elevated intracellular Ca2+ concentration was completely (TNP 5-10 mM, PCP 0.5 mM) or partly (PCP 1.0 mM) responsible for a concomitant increase in potassium permeability. No effects were found in connection with the weakly ionized 4-CI and 4-CI-3,5-di-CH3 derivatives at 1.0-5.0 mM and 0.5-2.0 mM, respectively. The fact that ionized phenols are able to transfer Ca2+ from water to a hydrophobic phase suggests that they may act as weak Ca2+ ionophores in the red cell plasma membrane.