A human lymphoblastoid cell line (Raji) developed macrocytosis after 5-7 days when cultured in the presence of 100, 250 and 500 mg ethanol/dl. The degree of macrocytosis was least with 100 mg/dl and greatest with 500 mg/dl. The macrocytosis was associated with a proportionate increase in the total protein content per cell, was reversed after culture in the absence of ethanol and was uninfluenced by the supplementation of the culture medium with 50 micrograms folic or folinic acids per millilitre. Ethanol also caused a substantial prolongation of the cell doubling time at concentrations of 250 and 500 mg/dl (but not 100 mg/dl) and this was associated with some increase in the proportion of non-viable cells in the cultures. Furthermore, ethanol increased the incorporation of 3H-leucine into protein per femtolitre of cell volume. It is proposed that the ethanol-induced macrocytosis may have developed as a consequence of the stimulation of the rate of protein synthesis within a normal or prolonged cell cycle.