The study of the immune system of mice of CBA (n=7) and C57BL/6 (n=7) strains was performed during a 12-hour photoperiod (12:12) and round-the-clock illumination (RI) in December and March. The numbers of CD3 +, CD4 +8 -, CD4 -8 +, CD4 +8 +, CD19 +, CD3+ hi lymphocyte subpopulations in the thymus and spleen, as well as the proliferative activity of thymocytes and splenocytes were measured by flow cytometry. It was found that the most pronounced interstrain differences in the cellular composition of the thymus were observed in March, while those in the cellular composition of the spleen were detected in December. Overall, in C57BL/6 mice as compared with CBA mice, the number and proliferative activity of the cells of lymphoid organs was increased. In December, the influence of RI on the cellular composition of the thymus was more pronounced in C57BL/6 mice, while the effect on cellular composition of the spleen was greater in CBA mice. In March, after exposure to RI, a number of CD3 +, CD19 + and CD4 +8 - splenocytes was increased in CBA mice, while it was decreased in C57BL/6 mice. In C57BL/6 mice, after exposure to RI, the proliferative activity of thymocytes decreased in winter and increased in spring. Interstrain and seasonal differences in the cellular composition of lymphoid organs in CBA and C57BL/6 mice, with a photoperiod of 12:12 and RI should be taken into account in experimental work with animals of different genotypes in different seasons of the year.