Neurones express several subtypes of intracellular Ca2+ channels, which are regulated by cytoplasmic calcium concentration ([Ca2+]c) and provide the pathway for Ca(2+)-induced Ca2+ release (CICR) from endoplasmic reticulum Ca2+ stores. The initial studies of CICR which employed several pharmacological tools (and in particular caffeine and ryanodine) demonstrated that: (i) caffeine induces intracellular calcium release in various peripheral and central neurones; and (ii) inhibition of CICR affects the parameters of depolarization-triggered [Ca2+]c responses. Experiments with caffeine demonstrated also that Ca2+ release from internal pools was incremental, suggesting the coexistence of several subpopulations of Ca2+ release channels with different sensitivity to caffeine. The CICR availability in neurones is controlled by both the Ca2+ content of the internal stores and the basal [Ca2+]c. Direct comparison of transmembrane Ca2+ influx with plasmalemmal Ca2+ current and [Ca2+]c elevation performed on sympathetic, sensory and cerebellar Purkinje neurones revealed the gradual activation of CICR. The efficacy of CICR may be regulated by the newly discovered second messenger cADP ribose (cADPR), although the mechanism of signal transduction involving cADPR is still unknown. CICR in neurones may be important in creation of local [Ca2+]c signals and could be involved in a regulation of numerous neuronal functions.