This investigation determined whether daily strenuous exercise would alter the progression and regression of an allogeneic lymphoid tumor in mice. We also determined if exercise would alter the cellular composition and vascularity of the tumor. Female Balb/c mice (H-2^d; age 6-8 weeks) were randomly assigned to sedentary control (CON) or daily exercised groups (EX). EX mice ran on a treadmill at incremental speeds (20-40 m^.min) for 3 hr or until fatigue. Each mouse was subcutaneously injected with 20 x 10⁶ EL-4 lymphoma (H-2^b) cells immediately after the first exercise bout (Day 1) and run daily. Tumor volume was measured daily using calipers. In some experiments, mice were euthanized on Days 5-10, 12, and 14. Tumors were excised and stained with hematoxylin and eosin or for Factor VIII associated antigen using immunohistochemistry and analyzed in a blinded fashion under a light microscope. There was no significant treatment main effect found for tumor volumes. Interestingly, a significant treatment x time interaction was found such that there was a two day delay in peak tumor volume and a more rapid tumor regression in EX. Tumors isolated from CON exhibited significantly higher numbers of apoptotic bodies, mitotic figures, blood vessels, macrophages (Ms), and neutrophils when compared to EX. Intra-tumoral lymphocytes were higher in CON early in tumor growth, but higher in EX at peak tumor size. These data indicate that daily strenuous exercise may influence tumor growth by affecting the microenvironment of the tumor, resulting in a delay in tumor growth and a more rapid regression.