The aggregation of blood platelets is a crucial step in normal hemostasis. Circulating platelets are sensitive to a variety of chemical and physiologic agents, some of which are formed or exposed in conjunction with vascular damage or endothelial cell denudation. Killer whale (KW) hemostasis appeared very intriguing, since drastic pressure changes are known to activate platelets, and yet these mammals have no untoward platelet reactions in response to pressure changes during or after diving to great depths, nor do they exhibit any abnormal bleeding associated with suboptimal platelet function. From the literature, it appears that most mammalian platelets fit one of two categories perhaps depending on the relative importance of the biochemical pathways in the stimulated cells. In one category, the phospholipase A₂ (PLA₂) pathway is well developed and platelet response following stimulation correlates with Thromboxane A₂ (TXA₂) production. In the other category, platelet aggregation can proceed with little or no dependence on TXA₂ production. KW platelets, in response to ADP (up to 20 uM), PAF (up to 10 uM), and 500 ug/ml Arachidonic Acid, appeared to aggregate normally during the first 2-5 minutes, but had completely disaggregated at 10 minutes after addition of agonist. Collagen (2-10 ug/ml) induced aggregation was normal and complete within 10 minutes. Aggregation in response to the calcium ionophore, A23187, was normal, while there was no aggregatory response to epinephrine or ristocetin. The collagen aggregation data would suggest TXA₂ production, and binding to receptors is normal in KW platelets. ADP, PAF, and arachidonate data show that KW platelets are initially very responsive to these agonists, but this responsiveness subsides in 2-5 minutes and the platelets appear to fail to secrete and irreversibly aggregate. Platelet receptor occupancy has been shown to be critical for aggregation in response to some agonists, and lower binding affinities for these agonists could explain the KW platelet response to ADP and PAF. The lack of an irreversible platelet aggregation response to arachidonate could indicate a cyclo-oxygenase abnormality similar to that seen in other species in which the arachidonic acid pathway is not well developed. KW platelets could add crucial data to aid in delineating the apparent multiplicity of biochemical pathways of platelet activation and aggregation.