Recent evidence indicates that A 2B receptors mediate cellular functions with potential clinical relevance. Both A 2A and A 2B receptors mediate vasodilation, and the receptor type involved depends on the vascular bed and species studied. In some experimental models, A 2B -induced vasodilation is mediated by the endothelium, but it is unclear whether this vasodilation is due to nitric oxide or whether A 2B receptors also mediate direct vascular smooth muscle relaxation. A 2B receptors expressed in smooth muscle cells inhibit their growth, raising the possibility that these receptors play a role in the vascular remodeling process observed in hypertension and atherosclerosis. A 2B receptors are also expressed in neurons, and there are several examples of these receptors mediating neuroexcitatory actions, including potentiation of neurotransmitter release. The highest expression of A 2B receptors is found throughout the intestinal tract. During diarrheal processes, neutrophils recruited into intestinal crypts release a soluble "neutrophil-derived secretagogue," which then increases intestinal secretion. It is now known that this neutrophil product is AMP, which is then converted to adenosine to activate A 2B receptors expressed in intestinal epithelium. It was also recently found that activation of human mast cells by adenosine is mediated by A 2B receptors. Mast cell activation is involved in adenosine-induced bronchoconstriction in asthmatics, suggesting that A 2B receptors are involved in this process. Our understanding of the functional role of A 2B receptors is hindered by the lack of selective agonist and antagonist of this receptor type. Recent studies suggest the feasibility of developing A 2B antagonists. Such agents may prove useful in the treatment of diarrheal diseases and in asthma.