We have tested the interaction between amyloid beta protein (A beta P) and tachykinin receptors in cultured UC-11MG astrocytoma cells, which express high affinity substance P receptors and respond to substance P with an unusually large stimulation of polyphosphoinositide hydrolysis. Both the full-length A beta P (A beta P1-40) and the fragment 25-35 (A beta P25-35) did not affect the stimulation of [3H]inositolmonophosphate (InsP) formation by substance P. A beta P25-35 was also inactive when applied to the cultures 18 or 72 h prior to the assay. In addition, A beta P25-35 did not displace specifically bound [3H]SarMet substance P from its recognition sites in intact UC-11MG cells. These results suggest that, at least in this specific cell type, amyloid peptides do not interact with substance P receptors.