Neuropeptide Y (NPY) is member of the family of tachykinins, and acts preferentially through the interaction with NK-2 tachykinin receptors. NPY is widely distributed and it is a potent stimulator of smooth muscle contraction, especially in the respiratory and gastrointestinal tract. Moreover, it has been demonstrated that NPY is able to influence the secretory activity of endocrine cells, and it may have a physiological role as regulator of endocrine functions. The role of NPY in the modulation of the pituitary–thyroid axis activity in the lizard, Podarcis sicula, was investigated by in vivo NPY administration. The effects were evaluated by examination of the morphological features of the tissue as well as by the measurement of TSH, T₄ and T₃ plasma levels. Intraperitoneally administered NPY (27 nmol /100 g body wt) decreased TSH plasma levels (from 4.81 ± 0.01 μUI/ml in carrier injected specimens to 1.23 ± 0.06 μUI/ml, 24 h after the injection).  T₄ plasma level strongly decreased from  5.18 ± 0.01 ng/ml in carrier injected lizards to 1.58 ± 0.02 ng/ml 24 h after the injection), and also T₃ levels were lowered from 4.00 ± 0.05 ng/ml in carrier injected specimens to 1.29 ± 0.02 ng/ml 24 h after the experimental treatment. Morphological observations showed clear signs of inhibition of the thyroid gland. All together, these results suggest that, in P. sicula, NPY may play a role in the modulation of the pituitary–thyroid axis activity.