AbstractPolypeptides solubilized from established normal and variant cell lines of Nicotiana tabacum L cv “Wisconsin 38” have been analyzed by one‐dimensional and two‐dimensional gel electrophoresis. There was little variability observed in the polypeptide profile in an established cell line; polypeptides present in different clonal lines of cells, all derived from an initial established cell culture, were very similar, if not identical. However, a large fraction of the observed polypeptides present in cytokinin‐habituated cell lines (up to 3.8% of the total polypeptides analyzed by two‐dimensional gel electrophoresis) were different from those found in the cytokinin‐requiring cells from which they were selected. The habituated nature of the selected cell lines was demonstrated to be epigenetic; tissue cultures that were reisolated from plantlets regenerated from habituated cell lines did require cytokinin. Further observations demonstrate: (1) that epigenetic events that alter a cellular phenotype change the expression of a relatively large number of polypeptides, (2) that a single epigenetic phenotype may be the result of any one of a number of possible patterns of gene expression, and (3) that epigenetic events are not