Optical aggregometry, traditionally used to assess platelet function, is highly dependent on sample preparation and technical procedure; as a result, data from various laboratories can be quite variable. In a study designed to assess the sources of variation, it was determined that the total standard deviation ranged from 3.6% to 7.7%. The assay variation by one analyst on one aggregometer on a single day ranged from 1.7 to 4.6. Day-to-day variation contributed 42% to 63% of the total variation, between-operator variation contributed 1% to 33% of the total variation, and within [between repeat measurements for a given sample by a given operator on a single day] variation contributed 22% to 36% of the total variation. Because of the disadvantages associated with optical aggregometry, alternate platelet function assays were considered and their correspondence to optical aggregometry was evaluated: activated clotting time, whole blood aggregometry, platelet count ratio, Platelet Function Analyzer (PFA-100, Dade), and Rapid Platelet function Assay (Accumetrics). Of those assays evaluated, activated clotting time and PFA-100 are assays that measure aspects of coagulation and hemostasis, whereas whole blood aggregometry, platelet count ratio, and RPFA are more closely related to platelet function. Each assay has value in monitoring various aspects of the coagulation process. The best method for monitoring safety and efficacy of various inhibitors of platelet function will ultimately be determined by clinical trials. (Am Heart J 1998;135:S170-S178.)