Background: Hydroxyethyl starch (HES) administration has resulted in decreased hemostasis and fibrinogen (FI)-thrombin-(FIIa)-Factor XIII (FXIII) interactions. I proposed to determine the hemostatic effect of hemodilution with PentaLyte (R) (6% HES, mean molecular weight 220 kDa) and Voluven (R) (6% HES, 130 kDa). Methods: Rabbits were intravenously administered 20 ml/kg PentaLyte (R) or Voluven (R) (n = 8 per fluid) over 10 min. Plasma was obtained prior to, 1 min and 1 h after hemodilution. Thrombelastography was performed, with clot initiation (R, sec), clot propagation (alpha, degrees), and clot strength (shear elastic modulus, G, dynes/cm(2)) determined over 20 min. Celite-activated samples had either no additions or addition of FI, FIIa or activated FXIII (FXIIIa) to restore protein content to pre-diluted values. Results and conclusions: While there were no significant differences between the groups, R significantly decreased 1 h after hemodilution compared with values observed before and 1 min after hemodilution, whereas alpha and G significantly decreased 1 min after hemodilution and then significantly, but only partially, increased 1 h after hemodilution compared with pre-dilution values. Addition of FI, FIIa and FXIIIa significantly decreased R in both groups. alpha and G 1 min after hemodilution were significantly enhanced by FI, FIIa, FXIIIa in both groups; however, 1 h after hemodilution, rabbits administered PentaLyte (R) had alpha and G enhanced only by FI and FXIIIa addition, whereas animals administered Voluven (R) had alpha and G significantly enhanced by FI addition. PentaLyte (R) and Voluven (R) hemodilution initially diminishes FIIa-FI and FXIIIa-fibrin, but within an hour primarily inhibit FXIIIa-fibrin interactions in the rabbit.