The NEU proto-oncogene encodes a 185,000 dalton transmembrane glycoprotein with extensive homology to epidermal growth factor receptor. In the current study the effect of exogenous NEU expression on phenotype and growth properties of cells established lines was examined. The replication defective retroviruses were used to express constitutively NEU cDNA in the Rat-1, NIH3T3 and Balb/c3T3 cells. In spite of the practically similar NEU mRNA and protein content in infected cells only in Balb/c3T3 cells, high NEU expression ultimately led to oncogenic transformation. The Rat-1 cells were practically insensitive to oncogenic action of NEU. Subpopulation divergency with respect to NEU-dependent transformation was also revealed in infected NIH3T3 cells. These results suggest the existence of unknown host-specific factor(s) determining the response of cells to NEU overexpression.