We describe a platelet defect characterised by absence of aggregation to adrenaline and lack of secondary aggregation to ADP and platelet-activating factor (PAF) in a male subject without a significant bleeding tendency. The platelets also exhibited a decreased response to the phorbol ester PMA and to vasopressin polypeptides.We obtained evidence that the defect did not involve the cyclooxygenase pathway and that it was not dependent on altered intraplatelet levels of cyclic AMP (cAMP). Furthermore, adrenaline-stimulated cAMP production was normal.Irreversible aggregation was obtained in response to a combination of two stimuli at subaggregating concentrations. This observation indicates that the lack of a bleeding tendency in this subject may be ascribed to subthreshold concentrations of agonists in vivo overcoming the defect to a single agonist.