The heavy metal bismuth induces a new type of selective neuronal degeneration that shares some common aspects with that seen following hypoxia and ischemia. Continuous application of 3 mu m bismuth to organotypic cultures of rat hippocampus resulted after 2-3 weeks in selective degeneration of CA1 pyramidal cells, while CA3 pyramidal cells, dentate granule cells, and subicular neurons were resistant. With 10 mu m bismuth, the majority of hippocampal neurons degenerated. The addition of 20 mu m MK-801, a noncompetitive NMDA-antagonist, during the entire culturing period failed to prevent neuronal degeneration induced by 3 mu m bismuth. GABA-immunoreactive interneurons were also affected by bismuth, but were generally less sensitive than CA1 pyramidal cells. Acute application of up to 100 mu m bismuth did not change the electrophysiological properties of CA1 pyramidal cells. (C) 1994 Wiley-Liss, Inc.