Depletion of brain serotonin by 5,7-dihydroxytryptamine (DHT) produces large changes in photic regulation of the hamster circadian running rhythm. This study documents the changes in daily wheelrunning caused by DHT lesions and their relationship to changes in photic conditions or food availability. Hamsters were given bilateral infusions of the selective neurotoxin during entrainment to a light-dark cycle (LD) of 14:10 h. At a later time, animals were transferred to constant light (LL) or dark (DD) for a prolonged period. Animals in DD were also subject to 3 days of food deprivation. Destruction of the serotonergic system does not change the amount of daily running in LD 14:10, but does alter the rate of running. Control animals respond to LL by greatly decreasing running compared to those with lesions. Food deprivation, a condition that greatly elevates running in control animals, is not nearly as effective in lesioned animals. The results suggest that serotonin-depleted hamsters have diminished responsiveness to environmental stimuli.