The aim of this study was to determine whether neural cells exposed to beta amyloid (A beta) activate the pentose phosphate pathway (PPP), a critical oxidative stress defense mechanism. A beta stimulated H2O2 production in neural (B12) and non-neural (HepG2) cells and stimulated PPP activity, the source of the main intracellular reductant NADPH, in HepG2 cells (67% increase). Catalase blocked the A beta-induced increase in PPP, demonstrating that H2O2 mediated the increase in PPP activity. B12 cells showed no increase in PPP following A beta exposure. Fifty-five per cent of HepG2 cells but only 11.1% of B12 cells remained viable after A beta exposure. Lack of PPP activation may contribute to A beta cytotoxicity in neural calls and may lead to differences in survival between neural and non-neural cells.