Hypertonic (7.5%) saline (HS) is advocated for resuscitation of injured and burned patients. Recent animal studies indicate that HS increases bleeding during uncontrolled hemorrhage, although the mechanisms for this are unclear. To investigate potential anticoagulant effects of HS (without dextran), normal human plasma was serially diluted with either HS or normal (0.9%) saline (NS). Prothrombin times (PT), activated partial thromboplastin times (APTT), and platelet aggregation studies were performed. Significant (p less than 0.05) deteriorations in clotting tests and platelet aggregation developed when 10% or more of normal plasma was replaced by HS, whereas there was no effect from similar NS dilutions. Strong correlations were observed between clotting test changes and sodium concentrations (R2 greater than 0.80, p less than 0.0001). Thus, HS exhibits anticoagulant activity, but not at the usual small volumes necessary to produce hemodynamic improvement. Nevertheless, the anticoagulant effect may be more pronounced with ongoing clotting factor losses or with the addition of dextran.