In vitro studies have shown that mild pressure increases red blood cell (RBC) aggregation. Enhanced RBC aggregation in pathologic states can drive the circulation into stasis. This investigation examined the effects of pressure on RBC aggregation in human volunteers. The hypothesis tested is that RBC aggregation is increased during hyperbaric exposure. Eleven subjects participated in dives to 300 feet of seawater (fsw) in a man-rated chamber complex. Blood samples were taken at the surface, at 66 fsw, and at 300 fsw. Data were analyzed with a repeated measures one-way analysis of variance for a complete randomized design. Statistical significance was achieved at P < 0.05. Data are expressed as mean +/- SEM. The median aggregate size (number of RBC/aggregate) of RBCs was significantly increased at depth. At a shear stress of 0.1 dyne/cm2, median aggregate size was 12.0 +/- 2.1, 33.0 +/- 7.3, and 48.8 +/- 10.8 at the surface, at 66 fsw, and at 300 fsw, respectively. These results show that mild pressure increases RBC aggregation in the human circulation.