We investigated, in a laboratory experiment, how natural food available in autumn influences the body mass, locomotor activity, and level of detoxification enzymes in the bank vole Clethrionomys glareolus (Schreber, 1780). In September and October 2001, two groups of bank voles were fed with herbs and acorns. A well-balanced mixed diet was a control. The animals fed with herbs showed high locomotor activity, compared to those fed control diet, a distinct increase of food consumption but loss of body mass. These voles also showed remarkably increased levels of detoxification enzymes (cytochrome P-450 and glutathione transferases) in their livers. Bank voles fed with acorns also lost weight and were more active, compared to the control (but less than the herb-fed group), and had higher levels of detoxification enzymes. Bank voles fed with the control diet showed the lowest level of locomotor activity and did not lose weight. We explain the increased activity of bank voles with stress response to low-quality food, especially as this effect ceased after changing the diet to the control one. Our results suggest that poor nutritional quality of herbs, the bank voles’ main food under natural conditions, may be the main cause of seasonal decline in vole density in autumn-winter.