A mutant human N-ras gene (codon 61, C to A substitution) was electroporated into the human leukemic cell line K562, originally derived from a patient with chronic myeloid leukemia (CML) in blast crisis. Despite confirmation of mutant N-ras gene integration and expression, mutant transfected cells exhibited no growth advantage when characterized in suspension cultures and clonogenic assays, and serum deprivation impaired proliferation of both normal and mutant N-ras transfected cells equally. A subclone containing a mutant N-ras gene displayed a proliferation rate and differentiation potential identical to that of non-transfected cells. The failure of N-ras mutations to modify K562 cell behavior is in keeping with the infrequent observation of N-ras mutations in blastic transformation of CML.