We studied the effect of thymopentin, a synthetic thymic peptide, on spontaneous behavior and stress models in BALB/c mice in which a WEHI 164 clone 13 murine fibrosarcoma had been implanted, as well as in the intact Sprague-Dawley rat. In untreated animals with tumors, spontaneous behavior was significantly inhibited. Resistance to swimming in cold water was also decreased in untreated animals. Thymopentin (10, 100, 1,000, and 5,000 micrograms/kg body weight, IP, 20 min before the test) enhanced spontaneous behavior in tumor-implanted mice. In addition, thymopentin partially restored floating capability of tumor bearers in either freely moving or animals on which an additional weight had been applied. In the latter test, plasma corticotropin and corticosterone levels were relatedly modified according to treatment. Rats treated with thymopentin showed a decreased sensitivity to painful stimuli. The effect of thymopentin was comparable to acetylsalicylate. Finally, thymic factors appeared capable of restoring the diminished behavioral activity of animals bearing tumors, as well as of increasing resistance to stressful stimuli and pain.