The reptile immune system is strikingly affected by seasonal variations, which induce changes in the structure of the lymphoid organs and in the function of the leukocytes. The aim of this work is to study several functions of splenic leukocytes from the turtle Mauremys caspica along its seasonal cycle. The functions assayed were adherence to substrate, mobility directed to a chemoattractant gradient (chemotaxis), lymphoproliferative response to mitogens, antibody-dependent cellular cytotoxicity, and natural killer-like cell-mediated cytotoxicity. Splenic leukocytes showed a positive response in all the assays, and this response was similar to that of mammals. In regard to the effect of the seasonal cycle, we have observed in winter a low adherence to substratum and high chemotaxis and cytotoxic activity, whereas in spring, only lymphoproliferation induced by mitogens showed high values except with lipopolysaccharide, which did not induce any seasonal variation in proliferation percentages. In summer, a high chemotaxis and cytotoxicity were observed, while in autumn, adherence to substratum was increased, but chemotaxis, cytotoxicity, and proliferation were clearly diminished. Our results demonstrate that splenic leukocyte functions are affected by the seasonal cycle, which induces a different pattern of response depending on the function studied.