Immunizing capacity of an interspecies somatic hybrid cell line, HyRA 4 (resulting from in vitro mating of R4/B malignant cells from the BALB/c mice, with normal embryonic cells of the South American rodent Akodon urichi venezuelensis), was compared with that of the parental R4/B cell line. Both R4/B and HyRA 4 cells displayed cross-reacting tumour specific transplantation antigen(s) and were able to induce a relative transplantation resistance against challenge inoculation of R4/B cells in syngeneic BALB/c mice. However, immunization with non-pretreated HyRA 4 hybrid cells carrying twice the number of R4/B chromosomes was not found to be more efficient than the immunization with X-irradiated R4/B parental cells in terms of the transplantation resistance induction. Furthermore, when mice in spite of pretreatment with either R4/B or HyRA 4 cells failed to reject the challenge graft, the resulting tumours showed enhanced growth rates as compared to those growing in non pretreated control mice. Though the HyRA 4 hybrid cells carried only a reduced number of chromosomes from the parental Akodon cell, they strongly displayed Akodon species specific antigen(s), thus rendering them unable to grow in normal BALB/c mice. In exceptional cases, in some mice in which tumours developed from the challenge inoculum of R4/B cells in spite of previous “immunization” with HyRA 4 cells, a delayed tumour outgrowth at the site of HyRA 4 inoculum was observed. These mouse tumour derivatives of HyRA 4 cells were, however, devoid of any detectable Akodon antigenicity as well as of any identifiable complete Akodon chromosome. This phenomenon resulting in the outgrowth of an antigenically “curtailed” hybrid variant is described and discussed.