Increased pressure, as may occur with hypertension, may alter cellular function by inducing repetitive mechanical strain. However, increased pressure itself may directly alter cellular function independent of stretching of cells. We undertook the present study to determine whether increased applied pressure could alter uptake of IgG complexes by macrophages. Increased pressure was applied to confluent macrophages grown on plastic culture plates using a pressure chamber apparatus kept inside the incubator at 37 degrees C and pressure regulated using a rotator pump and adjustable outlet valve. Macrophages that were subjected to increased pressure were found to have a significantly greater uptake of IgG complexes in a dose-dependent manner. The effect of increased pressure could be abrogated by carrying out experiments in calcium-free medium while this exerted no effect on uptake by macrophages under control conditions. Increased uptake of IgG complexes by macrophages subjected to increased applied pressure could also be attenuated by incubation with the calcium channel blockers amlodipine and cinnarizine. To determine whether the effect of increased pressure was related to the plastic substrate on which the cells are grown, cells were also seeded onto type I collagen gels and uptake of IgG complexes was measured. Uptake by macrophages on the type I collagen substrate was significantly enhanced with increased applied pressure compared to control (p < 0.01). These studies demonstrate that exposure of macrophages to increased pressure enhances their uptake of IgG complexes via a mechanism that appears to involve an increase in intracellular calcium. This effect might play a role in some of the consequences of systemic arterial and glomerular capillary hypertension.