Microglia are the resident immune cells of the central nervous system and become activated following infection or tissue damage. This is a complex process involving a phenotypic change associated with altered morphology, increased proliferation and migration towards the affected tissue, where the microglia release pro-inflammatory signalling molecules and become phagocytic. Microglial cells are known to express type 2 cannabinoid receptors (CB2), which are upregulated following activation and also enhance cell migration (Walter et al., 2003; Racz et al., 2008). Lower levels of the type 1 cannabinoid receptor (CB1) transcripts have been detected in microglia (Walter et al., 2008), but a function for these receptors remains to be demonstrated. In the present study we have used surface labelling immunohistochemical techniques to investigate CB1 and CB2 expression levels at the plasma membrane of cells from the BV-2 microglial cell line. Antibodies directed against surface epitopes of CB1 and CB2 receptors were initially validated against recombinant receptors expressed in HEK293 cells. They were then used to assess CB1 and CB2 expression in BV-2 microglial cells, using a cold-labelling protocol to minimise constitutive endocytosis. Under resting conditions, some light cell surface CB1 and CB2 immunoreactivity could be detected. However, following treatment with interferon gamma (100 ng/ml for 18-36 hours), there was a marked up-regulation in plasma membrane immunolabelling for both cannabinoid receptor subtypes. This was also associated with an increase in COX-2 expression, an established marker of microglial activation. Our findings that cell-surface CB2 protein is elevated following microglial activation are consistent with reported changes at the mRNA level. Moreover, a concomitant increase in surface CB1 receptor protein suggests that in addition to CB2, the CB1 receptor also has the potential to regulate microglial function, especially in the activated state.