Astrocytes are an important cell population in the CNS, involved in cytokine homeostasis and participating in a variety of important physiological and pathological processes. In the present study we showed that primary cultures of neonatal mouse cortical astrocytes stimulated with lipopolysaccharide (Balb/c mice strain, LPS: 1 microgram/ml, 18 h) or Theiler's virus, TMEV (SJL/J mice strain, TMEV: 10(5) PFU/well, 24 h) released an increased amount of nitrites (NO2-) and tumour necrosis factor-alpha (TNF-alpha) into the culture medium. Exogenous cannabinoids are known to modulate the function of immune cells. Anandamide, an endogenous ligand for the cannabinoid receptor, blocked the release of NO2- and TNF-alpha induced by LPS in a dose-dependent manner. In TMEV-stimulated astrocytes anandamide also suppressed, in a dose-related manner, the stimulatory effects of TMEV on both NO2- and TNF-alpha. It is suggested that anandamide exerts an immunoregulatory role in the CNS. These results could have important implications in the modulation of immunological and inflammatory processes by cannabinoid agents.