Previous studies indicate that the gaseous messenger carbon monoxide (CO) is released from the eye into the ophthalmic venous blood depending on the intensity of sunlight. This study was designed to determine whether the increased concentration of CO in ophthalmic venous blood affects the synthesis of melatonin and therefore, whether CO released from the eye under normal lighting conditions can be a carrier of light intensity information. Thirty six mature male wild boar and pig crossbreeds (n = 36) were studied. We measured the difference in the scotophase melatonin pathway response in terms of mean concentration of increased melatonin levels after 48 hours infusion of autologous blood plasma with an experimentally induced approximately 3-fold increase in the concentration of CO into the ophthalmic venous sinus. We demonstrated in this crossbreed a marked variation in the duration and amplitude of nocturnal melatonin peak in response to increased concentration of CO in ophthalmic venous blood. During the winter this treatment limited the nocturnal melatonin rise. During the summer this same experimental treatment enhanced the nocturnal melatonin rise. Changes in melatonin levels were always associated with parallel changes in AANAT protein levels. This work demonstrates that non-physiological changes in CO concentration in ophthalmic venous blood can have an acute impact on the systemic melatonin level. These results support humoral phototransduction as a mechanism for some of bright light's effects in animal chronobiology and treatment of winter seasonal affective disorder.