© 2014 John Wiley & Sons Ltd. Summary: Platelets are crucial subcellular elements of haemostasis at sites of vascular injury and are also known to be immune mediators in pathological thrombosis. Despite the integral role of platelets in many disease processes, there is very little information available on platelet function and response to agonists in healthy children. We recently reported important differences in the interaction of platelets with monocytes in the circulation, including increased formation of monocyte-platelet aggregates (MPAs) without concomitant increase in P-selectin expression. Our current study investigates parameters of platelet activation (PAC-1 binding and P-selectin expression) and MPA formation in response to a range of physiologically relevant platelet agonists in healthy children compared to healthy adults. All parameters were significantly higher in children in response to sub-maximal concentrations of thrombin receptor activator peptide and adenosine diphosphate, reflecting an age-specific difference in agonist-stimulated platelet reactivity in children. The results of our study challenge the general assumption that platelet reactivity in children is similar to adults. This finding is fundamental to investigating the role of platelets in diseases of childhood and pathogenesis of adult-based diseases that have their origins in childhood. Our findings underscore the need for age-specific reference ranges for platelet function in children rather than extrapolation from adult data.