Treatment of P3HR-1 Burkitt's lymphoma cultured cells with 4 mM n-butyrate for 48 h induced the abundant expression of a 35 000 dalton, microsomal membrane protein which was demonstrated to be the electrophoretically invariant Ii molecule. To prove this point, [35S]methionine-labelled, microsomal membrane proteins or immunoprecipitates of such detergent-solubilized proteins were subjected to electrophoresis either in SDS gels or in two-dimensional, nonequilibrium pH gradient gels. The induced p35 molecule was judged to be Ii by molecular weight and isoelectric characteristics and by immune complex associations. The abundant expression of Ii on butyrate-treated P3HR-1 cells mimicked the high level of expression of p35 or Ii on leukemic cells of a subset of patients with hairy cell leukemia. Alpha and beta chains of the HLA-D complex were absent from the P3HR-1 cell line and present in the Jijoye parent from which mutant P3HR-1 was derived. This relatively simple model can lead to the study of inducible synthesis, processing and expression of Ii, with or without HLA-D alpha and beta chains.