The influence of cytoplasmic acidification on dye-coupling between CA3 pyramidal neurons was examined by Lucifer yellow injections in guinea pig hippocampal brain slices. Neurons were believed to be acidified by exposure to 100 mM propionate. Dye-coupling was reduced significantly to 6% (n = 35) in propionate versus 28% (n = 39) in control solution (P less than 2%). Propionate may be a useful tool for experimental manipulation of coupling in the mammalian CNS.