Macrophages (Mph), monocytes, neutrophils, and lymphocytes (NK cells) are the principal types of effector cells of natural resistance (NR) in the defense of the host against tumor growth and dissemination of metastases. It has been shown that activated Mph can effectively destroy tumor cells in vitro and in vivo [10, 11], by producing several cytotoxic factors such as active forms of oxygen (the superoxide anion, singlet oxygen, hydroxyl radicals, and hydrogen peroxide), neutral proteases, tumor necrosis factor, and interleukins 1, 2, etc. [3, 13, 14]. Meanwhile, data have been published to show that Mph can potentiate the malignant properties of a tumor [6, 15-17]. It was shown previously that variants of cells of the STHE strain with low malignancy and spontaneously transformed in vitro, acquire malignant properties (tumorigenic and metastatic activity) during in vivo selection, and in addition, they acquire resistance to hydrogen peroxide (H202) and secrete an increased amount of prostaglandins E 2 on contact with NK cells [7, 9, 10]. We have shown that spontaneously transformed cells of the STHE strain, sensitive to the cytotoxic action (CTA) of activated macrophages, lose their sensitivity to the CTA of Mph . In order to examine the possible role of Mph and other effector ceils of NR in tumor cell selection in vivo, we attempted to carry out such selection in vitro, using as the selection factor, peritoneal exudate cells (PEC) of normal Syrian hamsters (resident PEC), and also PEC activated by bacterial lipopolysaccharide (LPS), and using parental cells of the STHE strain as the targets. The aims of this investigation were: 1) to attempt to obtain variants of STHE cells resistant to CTA of Mph by co-culturing them with resident and activated PEC in vitro; 2) to study the sensitivity of variants of STHE cells, selected with the aid of PEC, to the CTA of activated Mph and hydrogen peroxide.