Objective: To investigate the adrenal gland influence on diurnal rhythm of chronic inflammation induced by BCG in mice and its interaction with the pineal gland.¶Methods: C57Bl/6 mice were injected with BCG in the footpad and maintained in a 12/12 h light-dark cycle. All the experimental manipulations were done after 20-45 days. Paw swelling was measured every 4 h for 48 or 72 h and decomposed by Fourier transformation. Vascular permeability was evaluated by Evans Blue overflow, in mice killed at midday or midnight. 6-Sulphatoxymelatonin urine concentration was determined by radioimmunoassay in samples taken during the dark or light phase.¶Results: Adrenalectomy or metyrapone treatment abolished the paw swelling diurnal rhythm, the nocturnal reduction in vascular permeability, and the nocturnal increase in 6-sulphatoximelatonin in the urine. Nocturnal administration of melatonin to adrenalectomized mice restored the paw swelling diurnal variation and the reduction of vascular permeability of the inflamed paw.¶Conclusion: Adrenal cortical hormones are important for the maintenance of the diurnal rhythm of chronic inflammation (paw swelling and vascular permeability), probably by promoting a nocturnal surge of melatonin, which is the hor-mone that modulates the diurnal variation of chronic inflammation.¶