In women, cardiovascular morbidity and mortality sharply increase after the onset of menopause. There is substantial evidence that hormone replacement therapy (HRT) may decrease the risk of coronary heart disease (CHD); however, the mechanisms of this preventive effect are unclear. We investigated the association between HRT and plasma viscosity as well as fibrinogen levels in postmenopausal women of a population-based sample (n=300, age 52-65 years). A total of 94 women used HRT; of these, 50 took oestrogen monotherapy and 44 used oestrogen-progesterone combinations. HRT was associated with significantly lower fibrinogen concentrations (2.32 v 2.68 g/l, P<0.001) and decreased plasma viscosity (1.147 v 1.176 mPa/s, P=0.01). Multivariate analyses controlling simultaneously for the effects of age, smoking, body mass index, and use of diuretics confirmed decreased fibrinogen and plasma viscosity values in women using HRT. A trend towards lower plasma viscosity (1.139 v 1.160 mPa/s) and plasma fibrinogen (2.28 v 2.44 g/l) was observed in women on oestrogen-progesterone combinations as compared with oestrogen monotherapy users: however, after controlling for the above-mentioned variables these differences were not statistically significant. This study demonstrates decreased plasma viscosity in women on HRT. Improved rheology offers a mechanism by which HRT lowers the risk of CHD in postmenopausal women.