Platelets contain three types of secretory organelles: the dense granules, the alpha granules, and the lysosomes. Most of the proteins secreted from platelets are stored in the alpha granules, whereas the dense granules contain substances such as adenine nucleotides, serotonin, Ca++, and inorganic pyrophosphate types as well as a heparatinase. Three of the secreted alpha granule proteins have been measured by radioimmunoassay and it has been suggested that levels of these proteins in patient plasmas provide an index of in vivo platelet activation and secretion. These three are beta-thromboglobulin, platelet factor 4, and thrombospondin. In this chapter the chemistry of these proteins will be considered briefly, as will their clearance from the circulation, and then the clinical studies will be reviewed critically. Since radioimmunoassays were developed for these proteins (the first was reported in 1975), there has been a profusion of reports on levels of one or another of these proteins in a wide range of disease states, and these reports have indicated secreted platelet protein levels ranging from normal to grossly elevated in a given disease state. Possible reasons for such variability will be discussed.