The prion protein (PrPc) is a normal cellular protein expressed by neurones and astrocytes. An altered isoform, PrPSc is thought to transmit spongiform encephalopathies. Here we show that microglia also express PrPc. Sensitivity of microglia to activation is enhanced by increased expression of PrPc. Bacterial endotoxin increases superoxide production and inhibits profileration of microglia more effectively when microglia express PrPc. PrPc expression is therefore important for the normal function of microglia.