THE neurofibromatosis 1 (NF1) gene product, neurofibromin, is a tumor suppressor gene product capable of inhibiting the growth of cells in culture. If neurofibromin suppresses cell growth by arresting cells in G(0) or G(1), its expression might be regulated in a cell cycle-dependent fashion. In this study, we demonstrate that RAT-1A fibroblasts arrested in G(0)/G(1) by serum starvation and then released to progress through the cell cycle do not demonstrate significant changes in NF1 expression. However, when arrested in G(0)/G(1) by contact inhibition, NF1 expression in these cells is reversibly upregulated within 72 h, suggesting that NF1 expression is a late event associated with cell growth arrest which may contribute to the maintenance of the differentiated state.