The effects of suspending medium osmolality (166 to 836 mosm/kg) on flow in narrow bore tubes (33- to 146-microns diameter) were studied for 40% hematocrit suspensions of human red blood cells (RBC) in buffer; concurrent measurements of viscosity (eta r) and tube hematocrit (HT) allowed evaluation of the Fahraeus-Lindqvist effect (FLE) and Fahraeus effect (FE). The FLE and FE were present for all suspensions regardless of osmolality. Viscosity increased markedly for the hypertonic media, and the FLE was more pronounced for the hypertonic region; changes in eta r from 146 to 33 microns were -22% (220 mosm/kg), -34% (290 mosm/kg), and -45% (460 mosm/kg). In contrast, HT and hence the FE were relatively insensitive to osmolality (14% change over entire range of osmolality and diameter). Suspension viscosities in 33- and 146-microns tubes could not, in general, be accurately calculated using experimental HT values combined with eta r -HT data from 340-microns tubes; however, a semiempirical model indicated that 1) RBC number concentration in the tube and tube diameter per RBC volume are primary determinants of eta r, and 2) eta r can be predicted over a wide range of osmolalities and tube diameters. RBC transport efficiency was a function of both tube diameter and osmolality (maximum for 33 micron at approximately equal to 400 mosm/kg). Our results appear applicable to blood flow in nonisotonic regions of the circulation and to estimation of blood viscosity in microcirculatory vessels.