Freshly-isolated and cultured microglia display spontaneous and transient cytosolic Ca2+ elevations. Since there were no other cell types these preparations, spontaneous Ca2+ transients most likely occur due to intrinsic microglial signaling. Ca2+ transients originate from the endoplasmic reticulum and are dependent on the activity of phosphlipase C. Auto-/paracrine ATP release is not the trigger for spontaneous Ca2+ transients in microglia. Frequency and kinetics of Ca2+ transients are altered after prolonged LPS stimulation and in the context of glioma.