Physiological concentrations of the pineal hormone melatonin induce an increase of microtubules in neuroblastoma NIE-115 cells. This effect is due to an increase in the polymerization state of tubulin. Concomitantly, higher levels of soluble beta-tubulin are present in the treated cells. Unexpectedly, no significant changes in the levels of beta-tubulin or its mRNA occur in the presence of melatonin reflecting perhaps a strict control of its steady state in a physiological context. In contrast, higher amounts of microtubule-associated-protein 2 are found when the cells are exposed to melatonin. These findings support the idea that tubulin polymerization process is one of the targets of melatonin action. Furthermore, our results might explain the increase in the length and number of neurites present in these cells when they are treated with this hormone.