The ability of thymosin alpha1 (Talpha1) to prevent lung and breast cancer was investigated. Lung adenomas developed in A/J mice injected with carcinogens, such as urethane. The lung adenoma number was reduced by 15-45% if animals were daily treated subcutaneously (s.c.) with Talpha1 (0.4 mg/kg). Talpha1 (1 microM) directly inhibited the growth of mouse lung cell lines. These results suggest that Talpha1 may prevent mouse lung carcinogenesis because it directly inhibits the growth of lung cancer cells. Talpha1 prevented mammary carcinogenesis in two animal models. In the Fisher rat, an animal model of mammary cancer that is estrogen receptor dependent, tumors were initiated by the injection of N-methylurea (NMU). The rat survival was significantly increased by the daily injection of Talpha1. In the SV40T antigen mouse, a transgenic female mouse that spontaneously gets mammary cancer in an estrogen receptor-independent manner, survival was increased and tumor burden was significantly decreased by daily injection of Talpha1. These results indicate that Talpha1 is a chemopreventive agent in animal models for lung and breast carcinogenesis.