Besides microglia, astrocytes exert an important regulatory function in the initiation and control of neuro-inflammatory processes in the central nervous system. Clinical and experimental data suggest that sex steroids are neuroprotective and that neurological/neurodegenerative disorders display sex-specific characteristics. Astroglia is known to respond to toxic stimuli by secretion of distinct pro-inflammatory/apoptotic cytokines. In the present study, we investigated the influence of oestrogen and progesterone on the expression of the cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-18 in primary astrocytes obtained from neonatal mouse midbrain and cerebral cortex after the stimulation with lipopolysaccharides (LPS). LPS strongly induced the expression of TNF-alpha in astrocytes from both brain regions and IL-18 in those from midbrain. Oestrogen significantly attenuated LPS-induced TNF-alpha expression in the midbrain glia but not in the cortex glia. Combined treatment with oestrogen and progesterone together diminished LPS-induced IL-18 expression in the midbrain completely. Both steroid effects could be specifically antagonised by the steroid hormone receptor antagonists ICI 182 780 and mifepristone. We conclude that neuroprotective oestrogen and progesterone effects in the midbrain might be in part the consequence of a reduced pro-inflammatory response of astroglia.