Immunohistochemical expression of immunocompetent cells bearing major histocompatibility complex (MHC-II) and interleukin 2-R (IL2-R) (CD25) molecules was performed on lymph nodes with spontaneous postweaning multisystemic wasting syndrome (PMWS). Control lymph nodes displayed intense diffuse immunoreactivity to MHC-II in both follicles and interfollicular areas. A marked reduction of follicular MHC-II immunoreactivity and inconsistent staining of histiocytes in interfollicular areas was observed in PMWS cases with a slight lymphoid depletion; in those cases with moderate to severe lymphoid depletion, there was a progressive decrease in MHC-II expression. In controls and in slightly depleted nodes, IL2-R was equally expressed in interfollicular tissue and in follicles, whereas in moderate and severe cases, it was detected in interfollicular remnants only. Immunohistochemical staining was scored semiquantitatively. The mean MHC-II score was significantly reduced in PMWS cases compared with controls (Spearman test), whereas there was no difference in the IL2-R score. The evident reduction of MHC-II immunoreactivity suggests an impairment in MHC-II linked antigen presenting cell expression.