We showed previously that soluble low-molecular-mass tumor-associated antigens (TAA) could suppress chemically-induced tumorigenesis. In this study, we analyzed the mechanism of those findings. Studies were performed on the spleen and mammary gland tumors obtained from the following groups of rats: i) control rats treated with dimethyl-benz(alpha)antracene (DMBA), ii) vaccinated and carcinogen-treated rats with non regressed tumors, iii) vaccinated and carcinogen-treated rats with regressed tumors. Different zones of the spleen and tumors and their cellular content (Ki67+ and CD8+ cells, and macrophages) were analyzed morphometrically and immunohistochemically. Reaction of the spleen to vaccination was manifested in a significant increase in all areas of the white pulp and in a decrease in the size of the red pulp. The total number of cells in the white pulp (germinal center and PALS) and in the marginal zone was significantly higher in the spleen of rats with regressed tumors. The number of Ki67+ cells decreased significantly in both groups of vaccinated rats, but most prominently in the marginal zone and the red pulp in rats with regressed tumors. An increased number of CD8+ lymphocytes and macrophages was also seen in the red pulp. Different areas of the tumors (peripheral vs. inside at depth) showed different responses to vaccination and this difference was related to conditions of carcinogenesis, i.e. non-regressed vs. regressed tumors. In regressed tumors, all parameters studied were easily distinguishable in both areas of the tumors, while in non-regressed tumors, a marked distinction was seen only at their periphery. In regressed tumors, a negative correlation was seen at depth tumors between the number of Ki67+ cells and the number of CD8+ lymphocytes (r=-0.48). The findings indicated a strict antitumor effect of vaccination with the soluble low-molecular-mass TAA, which prevents the development of insufficiency of the immune system when an intensive immune reaction takes place.