Neurons, unlike glia and most other cell types, fail to express major histo compatibility complex (MHC) molecules, even in response to IFNgamma. This study shows that sensory neurons but not glia constitutively express high levels of suppressor of cytokine signaling-1 (SOCS 1), a negative regulator of IFNgamma signaling. Neurons from SOCS1 null mice expressed class 1 MHC in response to IFNgamma, while SOCS1 overexpression in glia inhibited M14C induction. Differential expression of SOCS1 by neurons explains their failure to express MHC. Regulation of SOCS I induction and therefore neuronal responses to IFNgamma may be critical for neuron survival following viral infection or injury. (C) 2002 Elsevier Science B.V. All rights reserved.