The objective of this study was to characterize and standardize whole blood electrical aggregometry (WBEA) in the pig and rabbit, animal models extensively used in atherosclerosis research, and to compare their platelet response with that of man. Platelet aggregation was studied in blood (WBEA) and platelet rich plasma (optical aggregometry, OA). Dose response curves were obtained for ADP and collagen. The effect of hematocrit on WBEA was also evaluated. Aggregation with ADP and collagen using WBEA was more extensive with human than with pig or rabbit platelets. OA revealed similar differences among species but the time to reach maximal aggregation was markedly shorter. Using WBEA, the extent of aggregation was inversely related to the hematocrit. We conclude that WBEA is a useful technique that may be of particular importance in situations where hyperlipidemic plasma prevents the use of OA, as occurs in some atherosclerosis research animal models.