The relative roles of two fundamental determinants of red cell deformability, namely cell size and cellular viscosity, in affecting red cell passage through narrow channels have been assessed by determining the filterability of red cells subjected to osmotic variations. Suspensions of red cells (10(6) cells/microliter) in eight different osmolalities ranging from 172 +/- 3 (mean +/- SD) to 665 +/- 28 mosmol/kg H2O were filtered through polycarbonate sieves with three different pore diameters (2.6 +/- 0.2, 4.5 +/- 0.6, and 6.9 +/- 0.8 micron). The mean corpuscular volume varied inversely with osmolality and ranged from 149 +/- 9 to 67 +/- 10 fl; the mean corpuscular hemoglobin concentration varied directly with osmolality and ranged from 23.7 +/- 0.8 to 55.9 +/- 3.9 g/dl. The filtration data were analyzed with a theoretical model to derive the parameter beta, which is the ratio of resistance in a pore bearing a red blood cell to that in a pore filled with the suspending medium alone. For each pore size, beta showed a V-shaped relationship with osmolality; the optimum osmolality for minimum beta varied inversely with the pore size. For the small 2.6-micron pores, the minimum beta was attained following hyperosmotic shrinkage of the red cells at 400 mosmol/kg H2O, whereas passage through the large 6.9-micron pores was facilitated by hypoosmotic swelling of the red cells in about 200 mosmol/kg H2O. Red cell filtration through small pores is more sensitive to alterations in cell volume, whereas that through large pores is primarily determined by changes in cellular viscosity.(ABSTRACT TRUNCATED AT 250 WORDS)