Terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) histochemistry is a sensitive method to expose DNA strand breaks in apoptotic cells, but it is difficult to conduct on slide-mounted sections. By using a 80 degrees C/0.5% Triton X-100 pretreatment, we have developed a TUNEL histochemical approach with high specificity and sensitivity using sections from ischemic rat brains. Thereafter, methamphetamine (METH)-induced neuronal death was investigated in mice brains. The results showed that a single injection of 40 mg/kg METH caused neuronal death in several brain areas including the striatum, cortex (frontal, parietal, and piriform), indusium griseum, medial habenular nucleus, and hippocampus. These results further confirmed the presence of METH-induced deleterious effects in nondopaminergic neurons. The significance of these findings is also discussed.