Mice with systemic lupus erythematosus (SLE) have unusual patterns of lymphocyte traffic characterised by diminished uptake of intravenously injected autoimmune cells into lymph nodes. This study examines the influence of the lymphocyte micro-environment on this aberrant migratory behaviour.To evaluate lymph node lymphocyte-endothelial interactions which can affect lymphocyte distribution without thein vivoinfluence of liver and spleen, thein vimhigh endothelial venule (HEV) binding assay was used. Lymph node HEV binding of autoimmune MRL-lpr/lpr (MRL/I) and MRL- +/+ (MRL/n) lymphocytes was increased when compared with CBA/T6 lymphocytes and contrasted with diminished lymph node uptake notedin vivo. This was independent of the lymph node source (MRL/I, MRL/n, CBA/T6) onto which the lymphocytes were overlaid. To examine the influence of the microenvironment onin vivotraffic,51Cr-labelled lymph node cells from normal CBA/T6 mice were injected into sex-matched MRL/l, MRL/n and CBA/T6 recipients. The distribution of cells was the same in each recipient strain suggesting that the micro-environment had little influence on the lymphocyte trafficking profiles of autoimmune mice. This study supports the view that aberrant lymphocyte migration in autoimmune mice results from defects intrinsic to the lymphocyte population and not the micro-environment.