The humoral function of the pineal gland is known to be strongly dependent on environmental lighting. Melatonin, the best characterized of the photo-dependent pineal hormones, has been reported to affect immune responses in mice. It has been hypothesized that the development of some types of psychosomatic and autoimmune diseases could be due to a disturbed release of this hormone. The present investigation was performed in order to evaluate effects of constant darkness (physiological stimulation of pineal melatonin synthesis) and constant light (physiological suppression of pineal melatonin synthesis) on the course of an experimental autoimmune model, the type II collagen-induced arthritis (CIA) in DBA/1 female mice. Mice kept in darkness develop more severe arthritis than those kept in constant light or in a normal dark/light rhythm (12 h light/12 h dark). Levels of anti-type II collagen antibodies were higher in mice kept in darkness, and the spleens of these animals were enlarged. Since castration of female DBA/1 mice enhances the severity of CIA, and since melatonin is known to exert effects on gonadal function, the experiment was repeated using oophorectomized mice. The same difference in arthritis severity between darkness- and light-exposed mice was obtained in this second experiment. We conclude that the exacerbation of arthritis in darkness is due to a darkness-induced change in levels of critical neurohumoral compound(s), that via gonadal independent mechanisms affect the autoimmune response. The exaggerated severity and chronicity of arthritis may be due to higher levels of melatonin in these animals.