Transmissible spongiform encephalopathies (TSEs) are neurological disorders that include genetic, infectious and sporadic forms of human Creutzfeldt-Jakob disease (CJD). The pathogenic agent is the prion protein that is composed of an abnormal isoform (PrPSc) of a host-encoded protein (PrPC). Analysis of the relative amounts of PrPSc glycoforms has been used to discriminate between various agents involved in TSE. The distribution and efficiency of conversion to PrPSc can be influenced by differences in the expression of PrPC. However, little attention has been given so far to the banding patterns of PrPC. Using four different antibodies recognizing amino- and carboxyl-terminal PrP sequences we analysed the glycoforms of PrPC in seven regions of the human brain using brains obtained from six subjects. For determination of the staining intensities, signals were quantified by densitometry and reproducible patterns were accomplished by many repeated immunoblot analyses. When amino-terminal binding antibodies were used for detection, PrPC in the frontal neocortex, nucleus lentiformis, thalamus, hippocampus and cerebellum displayed a glycotype with high staining of the diglycosylated isoforms. This was different from patterns in the pons and medulla oblongata, which showed a high intensity of the nonglycosylated isoform, and PrPC proteins, approximately 27 kDa in size, exhibited high staining using the carboxyl-terminal binding antibodies. This intense staining followed from an overlay of full-length and truncated PrPC isoforms. Furthermore, we found marked differences in the expression of PrPC. Variations in the processing of PrPC may lead to interregional differences in the glycoform composition of PrPSc in human brains.