Since melatonin has direct inhibitory effects on some tumor cells in vitro, the aim of the present work was to study whether the growth and structural characteristics of the human neuroblastoma cell line SK-N-SH in vitro are influenced by this indoleamine. Concentrations of melatonin of 10(-9) and 10(-11) M significantly inhibited (P < 0.05) cell proliferation. Subphysiological (10(-13) M) or supraphysiological (10(-7) and 10(-5) M) concentrations of melatonin lacked this effect. After 8 days of exposure to melatonin (10(-9) M), cells showed significantly smaller cell and nuclear sizes than control cells. Melatonin-treated cells presented greater neurite outgrowth than control cells. These results support the hypothesis that melatonin, at physiological concentrations, exerts a direct antiproliferative effect on SK-N-SH cells, promoting the differentiation of neuroblastoma cells.