Red blood cell aggregation induced by fibrinogen is a major determinant of the non-Newtonian flow behavior of blood and has been suggested as a possible contributing factor for thrombogenesis. Given the elevated fibrinogen levels and the incidence of thrombotic accidents in pregnancy, a study was designed to assess red blood cell aggregation at selected gestational periods. Three separate in vitro aggregation assays were used: (1) aggregation half time, (2) zeta sedimentation ratio, and (3) microscopic aggregation index. Our results indicate that red blood cell aggregation is increased throughout normal pregnancy (i.e., at 10, 25, and 36 weeks and during labor) in comparison to that in nonpregnant women. Significant correlations between plasma fibrinogen concentration and zeta sedimentation ratio (p less than 0.001) or aggregation half time (p less than 0.02) were demonstrated, but the correlation coefficient for the microscopic aggregation index technique did not reach significance (p greater than 0.20). Type O-positive red blood cells suspended in plasma from pregnant women also exhibited increased aggregation (p less then 0.001), thus suggesting plasma rather than cellular factors for the enhanced aggregation. Possible influences of abnormal fibrinogen structure during pregnancy are considered and the implications of increased red blood cell aggregation vis-à-vis altered blood viscosity are discussed.