The mechanical behavior of the neutrophil plays an important role in both the microcirculation and the immune system. Several laboratories in the past have developed mechanical models to describe different aspects of neutrophil deformability. In this study, the passive mechanical properties of normal human neutrophils have been further characterized. The cellular mechanical properties were assessed by single cell micropipette aspiration at fixed aspiration pressures. A numerical simulation was developed to interpret the experiments in terms of cell mechanical properties based on the Newtonian liquid drop model (Yeung and Evans, Biophys. J., 56: 139-149, 1989). The cytoplasmic viscosity was determined as a function of the ratio of the initial cell size to the pipette radius, the cortical tension, aspiration pressure, and the whole cell aspiration time. The cortical tension of passive neutrophils was measured to be about 2.7 x 10(-5) N/m. The apparent viscosity of neutrophil cytoplasm was found to depend on aspiration pressure, and ranged from approximately 500 Pa.s at an aspiration pressure of 98 Pa (1.0 cm H2O) to approximately 50 Pa.s at 882 Pa (9.0 cm H2O) when tested with a 4.0-micron pipette. These data provide the first documentation that the neutrophil cytoplasm exhibits non-Newtonian behavior. To further characterize the non-Newtonian behavior of human neutrophils, a mean shear rate gamma m was estimated based on the numerical simulation. The apparent cytoplasmic viscosity appears to decrease as the mean shear rate increases. The dependence of cytoplasmic viscosity on the mean shear rate can be approximated as a power-law relationship described by mu = mu c(gamma m/gamma c)-b, where mu is the cytoplasmic viscosity, gamma m is the mean shear rate, mu c is the characteristic viscosity at characteristic shear rate gamma c, and b is a material coefficient. When gamma c was set to 1 s-1, the material coefficients for passive neutrophils were determined to be mu c = 130 +/- 23 Pa.s and b = 0.52 +/- 0.09 for normal neutrophils. The power-law approximation has a remarkable ability to reconcile discrepancies among published values of the cytoplasmic viscosity measured using different techniques, even though these values differ by nearly two orders of magnitude. Thus, the power-law fluid model is a promising candidate for describing the passive mechanical behavior of human neutrophils in large deformation. It can also account for some discrepancies between cellular behavior in single-cell micromechanical experiments and predictions based on the assumption that the cytoplasm is a simple Newtonian fluid.