Although diltiazem improves function in several organs following trauma-hemorrhagic shock, the mechanism remains unknown. It is hypothesized that diltiazem maintains red blood cell calcium-to-magnesium ratio, resulting in better deformability of red blood cells. This should reduce blood viscosity, allowing red blood cells to traverse the microcirculation more efficiently and improve tissue oxygenation. To study this, rats (n = 23) underwent cannulation of various blood vessels and were divided into five groups: Group 1, control rats which had surgery only; Group 2, sham-operated rats which were not hemorrhaged but were infused with a volume of lactated Ringer's solution (LRS) equivalent to that given to the hemorrhaged animals (Groups 4 and 5); Group 3, hemodilution animals which were maintained at normal blood pressure but with the hematocrit lowered to values equivalent to hemorrhaged rats (Groups 4 and 5); Groups 4 and 5, animals which underwent fixed pressure (40 mm Hg) hemorrhage, followed by resuscitation with LRS, 5x the shed blood volume, and were given IV saline (Group 4) or 400 micrograms diltiazem/kg (Group 5) with the resuscitation. Blood viscosity was measured at the end of resuscitation with a Brookfield DV-III viscometer. Results showed that blood viscosity was markedly reduced in the diltiazem treatment group, but was unchanged in any of the other groups versus the control. Thus, the beneficial effects of diltiazem after trauma-hemorrhage and resuscitation may be due in part to the marked decrease in blood viscosity allowing for improved oxygen delivery and removal of metabolites.