The effect of mesna on intracellular accumulation of cytosine arabinoside (Ara-C) in murine normal and neoplastic lymphocytes was studied. Simultaneous exposure of cells to mesna at concentrations ranging from 0.25 to 1.0 mM and 3H-Ara-C (40.0 nM) resulted in a strong inhibition of Ara-C uptake in normal lymphocytes. Under the same experimental conditions, mesna did not affect the Ara-C uptake in neoplastic cells (cultured L5178Y mouse leukaemia cells and neoplastically transformed thymus cells). It was found that the inhibitory effect of mesna was not cell cycle-dependent, since mesna reduced the Ara-C uptake in both normal quiescent and PHA-stimulated cells. We therefore concluded that mesna may selectively reduce Ara-C uptake by normal cells in vitro.