Deficiencies of Ca2+homeostasis are proposed to play an important role in neuronal ageing and/or neurodegeneration. The aim of this study was to investigate, in a defined neuronal population, primary cerebellar granule neuron culture, the time-dependent changes in Ca2+homeostasis and compare them with data obtained in cerebellar brain slices from aged rats. In neurons aged in culture (DIV 23), a small decrease in the resting [Ca2+]iwas associated with a decrease in the maximal rate of [Ca2+]iincrease upon KCl-induced depolarization and in the amplitude of the [Ca2+]iresponse, when compared with mature neurons (DIV 9). The most significant change of [Ca2+]isignal parameters was a 50% decrease in the rate of [Ca2+]irecovery after the stimulation. These results were similar to those obtained in aged brain slices, and indicate that primary neuronal cultures could serve as a model for studying the age-related changes in Ca2+homeostasis.