We studied the effect of chronic intraperitoneal (ip) administration of serotonin (5-HT) and thyroid function. We injected daily intraperitoneally for 10 days different doses of 5-HT, and measured plasma thyroid hormones and TSH levels. There was a decrease in the plasma levels of T3 and T4 with medium doses of 5-HT (0.2 and 0.4 mg/Kg bw for T3, and 0.2 for T4). No effects were evidenced on the plasma levels of TSH. In normal environmental conditions, the site action of 5-HT outside the blood-brain barrier is active when the 5-HT is injected at defined doses. This is probably a result of down-regulation independent of the hypothalamus-pituitary-thyroid axis.