The effect of L-methionine substitution by L-homocysteine on the growth in vitro of three normal and seven neoplastic cell lines has been examined. Although homocysteine alone was insufficient to support growth of some of the tumour cells an increased growth rate was observed in the presence of homocysteine when the methionine concentration in the medium became growth limiting. The ability to proliferate in such deficient media correlated with the minimal concentration of methionine sufficient to sustain optimal growth rates. This suggests that the inability of some tumour cells to grow under such nutritional conditions is due to the homocysteine-transmethylase being insufficient to meet the methionine requirements of the cell.