Methionine dependence is the inability of cells to grow when methionine (Met) is replaced by its immediate precursor homocysteine (Hcy) in the culture medium (Met-Hcy+ medium). All normal unestablished cell strains tested to date have been shown to be methionine-independent and thus grow almost as well in Met-Hcy+ medium as they do in Met+-Hcy-medium. Results presented here indicate that out of 23 cell lines derived from diverse types of human tumors, 11 do not grow at all in Met-Hcy+ medium and are absolutely methionine-dependent and 3 grow only slightly in this medium. Many of the tumor cell lines tested have little else in common other than the fact that they are methionine-dependent. The high frequency of occurrence of methionine dependence in diverse types of human tumor cells indicates that methionine dependence may be an important aspect of oncogenic transformation and therapeutically exploitable.