To learn about the mechanisms of excitotoxic cell death in vivo, three different excitatory amino acid receptor agonists (kainic acid, quinolinic acid or quisqualic acid) were injected in the left striatum of adult rats. Brains were examined at 24 and 48 h after injection. Morphological and biochemical studies were performed using conventional stains, histochemistry, in situ labelling of nuclear DNA fragmentation, and agarose gel electrophoresis of extracted DNA. Large numbers of cells with cytoplasmic shrinkage and nuclear condensation or granular degeneration of the chromatin, and fewer cells with apoptotic morphology were distributed at random in the injured areas of the three groups of treated animals but not in rats injected with vehicle alone. A ladder pattern, typical of internucleosomal DNA fragmentation, was observed 24 h after treatment. This was replaced by a smear pattern, consistent with random DNA breakdown, at 48 h. These morphological and biochemical results suggest that prevailing necrosis together with apoptosis occur following intrastriatal injection of different excitotoxins.