The osmotic permeability coefficient (Pf) was measured with a stopped-flow light-scattering technique. There is an artifactual light-scattering signal produced by the initial mixing that decays with a half-time of ~0.2 s. This seriously interferes with the measurement of the osmotically induced change in cell volume, which has a similar half-time. This "injection artifact" is associated with the biconcave shape of the cells. It is negligible for cells that have been made nearly spherical by swelling them in 160 mosmol. The dependence of this artifact on the cell volume may explain the previously observed dependence of Pf on the cell volume. When cells are made echinocytic (and therefore spherically symmetric), this injection artifact becomes negligible at all cell volumes and Pf can be accurately measured. The Pf of echinocytic cells was nearly constant, varying by <10% with the direction of flow and the medium osmolarity (160-360 mosmol). The average value of Pf was 2.0 × 10-2 cm/s (T = 23°C).