BACKGROUND: High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES. METHODS: A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model. RESULTS: The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831). CONCLUSION: Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected.