Since melatonin causes considerable reduction in the thymic weight of chickens, the aim of the present study was to find out whether the bursa of Fabricius and the immune response are also affected by this substance. The results show that melatonin also acts on the bursa of Fabricius depending upon the administration route. When injected subcutaneously it does not reduce bursal weight and the histological pattern does not change, while primary and secondary immune responses are significantly lowered. When melatonin is introduced into the bursa, it causes a considerable decrease in bursal weight and the histological pattern is greatly modified. A significant reduction in antibody production is observed involving the primary immune response alone. Transmission electronic microscopy seems to show that melatonin affects the reticulo-epithelial (REp) cells.