Immunostaining for prion protein (PrP) using the KG9 monoclonal antibody was undertaken on brain sections from an unselected group of 200 post-mortem cases. One case of clinically diagnosed vCJD was confirmed and showed widespread abundant PrP immunostaining with KG9 and somewhat less abundant PrP with another monoclonal antibody, 3F4. PrP immunostaining seen with KG9 was insensitive to proteinase K pretreatment in sections from this case of vCJD. Among the remaining 199 cases, sections from 84 (42%) showed small amounts of PrP immunoreactivity with the KG9 antibody, mainly localized to neurones, neural processes and argyrophilic plaques of the type seen in ageing and Alzheimer's disease. Purkinje cells, swollen (ischaemic) axons, macrophages and microglials cells were also occasionally labelled with this antibody in non-CJD cases. Pre-treatment of adjacent sections from non-CJD cases with positive KG9 staining abolished this staining, indicating that it represented the cellular form of PrP. There were differences in age, sex and cause of death in non-CJD cases with some PrP immunostaining patterns compared with cases lacking any staining. Specifically, a younger mean age, more females and fewer cardiac deaths were found among those with neuronal PrP staining patterns. Staining of some features was also significantly associated. These findings need to be taken into account when PrP immunostaining is used to diagnose prion diseases. They may indicate that cellular PrP is increased in the human brain under some circumstances and provide insight into the handling of this protein by human brain cells.