ACIDOSIS is a well established concomitant of tissue ischemia. Acidosis in the pH range 6.0–7.0 is seen in cerebral ischemia and within solid tumors. Extracellular acidosis of pH 6.0 and 6.4 provided essentially complete protection from & h serum deprivation induced apoptotic death of cultured primary murine neurons. We tested the effect of p53 using transformed mouse embryo fibroblasts of either p53+/+or p53−/−genotype. Both were markedly protected from serum deprivation by acidity. Hypoxia induced fibroblast injury was also reduced at pH 6.8. Lower pH resulted in a shift from apoptotic to necrotic morphology after 24h hypoxia. Acidosis reduces apoptosis of both normal and transformed cells, irrespective of p53 status.