In the mouse a series of experiments were carried out which suggested that one or more mast cell contents might produce constriction of pial arterioles. Local application of 48/80, a compound known to release some of the mast cells contents, produced pial arteriolar constriction. Pretreatment designed to deplete the mast cell contents prior to testing of vascular reactivity, blocked the local response to 48/80 while leaving the response to another contractile agent intact. The data suggest that 48/80 produces pial vasoconstriction by releasing one or more contents from mast cells in the arachnoid membrane. Alternatively, the local constrictor effect of 48/80 may be independent of pial mast cells, but inhibited nevertheless by prior release of materials from mast cells elsewhere in the body.