Activation of α-adrenergic, muscarinic, serotonergic, glutamatergic, and P 2y -purinergic receptors together with a host of peptides cause the hydrolysis of polyphosphoinositides (PPI) in astrocytes, leading to diacylglycerol (DAG) formation and intracellular calcium mobilization. Using a combination of NO-chemiluminescence detection and vascular ring bioassay, it is demonstrated that bradykinin and calcium ionophore evoke the release of a vasorelaxant nitrosyl compound from astrocytes grown on microcarrier beads. In addition to bradykinin, a variety of agents (amines, purines, and peptides) are reported to evoke release of endothelium-derived relaxing factors (EDRF) with NO-like properties. Astrocytes are responsive to many of these agents but lack receptors for N-methyl-D-aspartate (NMDA). All of the agents that evoke the release of ADRF, activate receptors linked to PPI hydrolysis and calcium mobilization. One major role of astrocytes associated with the vasculature is the induction of changes in endothelial permeability. These studies indicate that products of astrocytes could both directly evoke changes in the release of PGI, from cerebral micro vessel cells, and also modulate the stimulated release of this vasodilator.