Although the rheologic behavior of sickle erythrocytes (SS cells) is highly dependent on oxygen tension (pO2) and temperature, very little data exist regarding the effects of deoxygenation and reoxygenation on the rheology of “individual” SS cells at body temperature. We have devised and assessed a new experiment system, in which micropipette aspiration can be performed on individual cells in a constant- temperature chamber that has ports for changing media with different pO2 (effected in 30 to 120 seconds) and sensing probes for monitoring pO2 and temperature. This system enabled us to simultaneously alter and monitor pO2 at 37 +/- 0.5 degrees C, and to monitor and study a single cell under microscopic observation. The static rigidity (E) and dynamic rigidity (eta) of individual SS cells were determined by repeated aspirations of the same cell under various pO2. With stepwise reductions in pO2, E and eta showed no significant changes before sickling, but once sickled, their values markedly increased by 10(2)- to 10(3)-fold concomitantly with morphologic alteration of the cell. Thus, the deformability of a single SS cell behaves in an “all or none” manner at a critical pO2, and earlier studies on the effect of deoxygenation on the rheology of SS cell suspensions probably reflect the overall behavior of SS cells with widely distributed critical pO2.