Basophils and mast cells (Fc epsilon RI-bearing cells) play important but clearly distinct roles in human inflammatory and allergic reactions. While many similarities have been described, it is increasingly evident that many more differences exist between these two cell types. These include maturational and ultrastructural as well as functional differences. Basophils and mast cells can be activated by different stimuli, produce different profiles of inflammatory mediators, and their response can be modulated in a different fashion. The heterogeneity of Fc epsilon RI-bearing cells has recently been extended by studies on mast cells isolated from different human tissues. These studies may suggest the existence of different human mast cell phenotypes the development of which may be regulated by microenvironmental factors. A better understanding of the heterogeneity of basophils and mast cells is a necessary step to define their respective roles in the pathophysiology of human inflammatory responses.