The purpose of this study was to compare the macrocirculatory and microcirculatory effects of simvastatin in hyperlipemic patients. In vitro measurements of lipoprotein levels and macrocirculatory hemorheology were complemented by in vivo measurements of the pulmonary capillary red cell volume (RCVpc) before and after 6 weeks of treatment with 40 mg of simvastatin daily in 30 male patients with hyperlipoproteinemia type IIa. RCVpc was assessed from the vascular component of the lung diffusing capacity for carbon monoxide, using the modification of the Roughton-Forster's method. RCVpc was increased in patients (60.9+/-9 versus 40+/-9 ml in healthy controls) and it decreased to 47+/-6 ml after treatment (P=5x10(-11)). The decreases in RCVpc correlated to concomitant decreases in peripheral hematocrit (R=0.68) and serum total cholesterol (-34% on average; R=0.59). Membrane diffusing capacity was normal in patients and not affected by the therapy; suggesting that increased RCVpc was due to increased micropulmonary hematocrit. Thus, it appears that viscosity in microcirculation is greatly increased in hyperlipemic patients and that simvastatin is able to normalize it. Since microcirculatory conditions can only partly be inferred from in vitro measurements the use of lung diffusional parameters was advocated, which enable in vivo assessment of hemorheology in microcirculation.