By electron microscopy tubulovesicular structures (TVS) have been consistently observed in brain tissue of transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced, but not naturally occurring, Creutzfeldt-Jakob disease (CJD). For the first time we report here the presence of TVS in human brains with CJD as detected by transmission electron microscopy. TVS were observed in all three CJD specimens (two biopsies, one autopsy), but they were rare and were found only in one or two location(s) per grid. TVS were seen in distended pre- and postsynaptic terminals and measured approximately 35 nm in diameter; they were smaller and of higher electron density than synaptic vesicles. Their occurrence in all types of transmissible spongiform encephalopathies irrespective of the affected host and the strain of the infectious agent suggests their biological significance.