A cone-and-plate viscometer was used to study shear-induced aggregation in whole blood. Aggregate size distribution curves were measured from samples subjected to controlled shear rates for varying time intervals. Blood samples in heparin, but not in citrate, developed aggregates at shear rates below 500 sec-1. These aggregates disintegrated at 1000 to 2000 sec-1. There appears to be a donor-specific threshold shear rate, above which significant amounts of shear-induced aggregation were found. For normal donors this threshold is in the range of 2000 to 3000 sec-1 for exposure times of 1 min. The extent of aggregation and the stability of aggregates formed increased with both shear rate and the shear time. Above the threshold shear rate, less than 6 sec exposure time was sufficient to trigger aggregation. Aggregates generated by exposing blood to shear above these levels for 30 to 60 sec were stable for at least 5 min. Blood in heparin was more sensitive to shear than that in citrate. Whole blood was more sensitive to shear than platelet-rich plasma. An ADP-utilizing enzyme system, creatine phosphate/creatine phosphokinase, was effective in reducing both sensitivity to and stability of shear-induced aggregation. Creatine phosphate alone was partially effective, whereas creatine phosphokinase alone was ineffective. This indicates that ADP released from cellular components in blood plays a positive role in shear-induced aggregation.