Hypoxic episodes, induced by chronic respiratory disease or stroke, increase the probability of the sufferer developing Alzheimer’s disease (AD) as they age. Although the mechanisms underlying this observation are unknown, we have previously shown that hypoxia causes dramatic remodelling of cellular Ca²⁺ homeostasis by increasing Ca²⁺ influx through voltage-sensitive and insensitive ion channels and by modifying cellular Ca²⁺ buffering of store-mediated Ca²⁺ release (Scragg et al, 2005; Smith et al, 2005). Additionally, Ca²⁺ dyshomeostasis has been implicated in the neurodegeneration of AD, and hypoxic disruption of Ca²⁺ signalling has been linked to pro-amyloidogenic processing. Investigations of the role of Aβ peptides (Aβ) in these changes using synthetic monomers have produced contradictory results. A possible explanation for this has been the recent observations that many of the cytotoxic effects of Aβ are due to soluble oligomers of Aβ (Walsh and Selkoe, 2004). Therefore, we investigated the effects of hypoxia and soluble oligomers of Aβ on bradykinin (BK)-induced Ca²⁺ release in primary cultures of astrocytes and a neuroblastoma cell line, SH-SY5Y loaded with fura-2 AM. Chronic hypoxia (1% O2, 24hr) caused a significant (>2fold) increase in the size of the BK-induced Ca²⁺ response relative to normoxic controls in both cell types. O2 concentrations closer to physiological (9%) than atmospheric (21%) had no effect on BK-induced rises in [Ca²⁺]_i. Conditioned media (CM) from CHO cells stably expressing human APP751 containing the V717F mutation (7PA2 cells; a gift from D. Walsh) which secrete Aβ was tested to ensure that it contained Aβ monomers and oligomers and then applied to cells for 24hr. Treatment with 7PA2 CM caused a large (~2fold) increase in the BK-evoked Ca²⁺ transient in both astrocytes and SH-SY5Y cells. Treatment with CHO CM had no effect. Neither hypoxia nor soluble Aβ oligomers had any effect on capacitative calcium entry. These results confirm the ability of chronic hypoxia to modulate Ca²⁺ signalling in different cell types, supporting previous studies. The modulation of Ca²⁺ homeostasis by Aβ oligomers contributes to growing evidence suggesting this aggregation state to be important in neuronal dysfunction in the early stages of Alzheimer’s disease. These results also suggest Ca²⁺ dyshomeostasis as a possible mechanism by which Aβ oligomers exert their toxicity. The observation that CCE is unaltered by either treatment suggests that, as with hypoxia, Aβ oligomers may act on Ca²⁺ extrusion and buffering mechanisms rather than directly on the Ca²⁺ stores.