Microvesicle particles (MVP) are bioactive subcellular particles which have been recently implicated in the keratinocyte response to many environmental stressors including ultraviolet B radiation (UVB). Previous studies have demonstrated that UVB generates high levels of MVP in a process involving the platelet-activating factor receptor (PAFR) and the enzyme acid sphingomyelinase (aSMase). Yet the fluences of UVB needed to generate MVP are usually above those commonly encountered. Using models including human epithelial cell lines in vitro, human skin explants ex vivo and murine studies in vivo, the present studies indicate that pretreatment of epithelial cells/skin with PAFR agonist/phorbol ester can synergize with low fluences of UVB to generate high levels of MVP. These studies indicate the possibility that MVP could play a role in combinatorial pathologic processes involving UVB.