Tumour necrosis factor (TNF)-α, a strong immune mediator, is released within the brain during inflammatory diseases and contributes to immunological activation of glial cells. Here we report that, in astrocytes, TNF-α also affects the intracellular Ca2+ homeostasis and basic electrophysiological properties such as the membrane potential. Using the Ca2+ indicator dye fura-2 in a cell culture model, we found that TNF-α (10–1000 U ml⁻¹), but not interleukin 1 or 6, induced a slow but more than two-fold increase of the intracellular Ca²⁺ concentration, which could be blocked by Co²⁺ (1.0 mM), verapamil (100 μM) or omission of external Ca²⁺. This intracellular Ca²⁺ increase was accompanied by a marked decrease of the membrane potential by 35 mV. CSF of patients with bacterial meningitis, known to contain large amounts of TNF-α, induced a similar depolarization of astrocytes, which was markedly reduced by a neutralizing anti-TNF-α antibody. We conclude that TNF-α induces an increase of intracellular Ca²⁺ and a depolarization in astrocytes with the consequence of disturbing voltage-dependent glial functions such as regulation of local ion concentrations and glutamate uptake. During inflammatory CNS diseases this immuno-electrical coupling may contribute to an impairment of neuronal function.