Alpha-melanocyte stimulating hormone (alpha-MSH) was originally documented as a peptide that induced pigmentation in skin. However, more recent work suggests that it acts as a potent anti-inflammatory molecule in several tissues including nerve. Alpha-MSH works by directly inhibiting cytokines that cause inflammation, in particular tumour necrosis factor-alpha, interleukin-1beta, interleukin-6 and gamma-interferon. A common mechanism of inhibition is via the NF-kappaB transcription factor. We investigated the ability of alpha-MSH to inhibit the activation of NF-kappaB in cultured rat primary olfactory ensheathing cells stimulated with tumour necrosis factor-alpha or gamma-interferon. Both cytokines activated NF-kappaB rapidly (after 60 min incubation), observed as a translocation from cytoplasm to nucleus. alpha-MSH inhibited this activation (and hence nuclear translocation) by approximately 50% for both cytokines. The anti-inflammatory properties of this peptide in neural cells may therefore support a basis for treating CNS injury, where inflammation is a major problem.