In vivo administrations of anti-Lyt-2.2 (CD8) mAb and anti-L3T4 (CD4) mAb selectively eliminated CD8+ cells and CD4+ cells, respectively. The relative potencies of CD8+ cells and CD4+ cells and their roles in primary tumor rejections were studied by investigating the effects of these mAbs on tumor growth. CD8+ cells were themselves fully capable of mediating rejection in 5 different tumor rejection systems: two radiation leukemia virus (RadLV)-induced leukemias, B6RV2 and BALBRVD, a radiation-induced leukemia BALBRL male 1, and a plasmacytoma BALBMOPC-70A in CB6F1 mice, and a Friend virus-induced leukemia B6FBL-3 in B6 mice. On the other hand, CD4+ cells were capable of resisting tumor growth of B6FBL-3, but not of the other four tumors. Furthermore, for efficient rejection of CB6F1UV female 1 sarcoma by CB6F1 mice, synergy of CD8+ and CD4+ cells was necessary. Blocking of UV female 1 rejection was abrogated by delayed administration of anti-L3T4 (CD4) mAb but not anti-Lyt-2.2 (CD8) mAb, indicating the involvement of CD4+ cells in only the initial phase of rejection.