Siberian hamsters breed during the long days of spring and summer when environmental conditions (e.g., ambient temperatures, food availability) are favorable for reproduction. Environmental conditions may also influence the onset and severity of infection and disease, and photoperiodic alterations in immune function may comprise part of a repertoire of seasonal adaptations to help survive winter. In order to test the hypothesis that animals use day length to anticipate seasonal stressors and adjust immune function, we measured antigen-specific delayed-type-hypersensitivity (DTH) responses in the skin of male and female hamsters during long, "summer-like," or short, "winter-like" days, at baseline and following acute restraint stress. Sex steroid hormones were lower, and cortisol was higher, in males and females during short days. Baseline DTH was enhanced in short- compared to long-day males, and acute stress augmented this effect. In contrast, photoperiod alone did not influence the DTH response in females. As predicted, female hamsters exhibited significantly higher DTH responses than males during long days, but not during short days. However, this enhancement was observed in acutely stressed females only. Cortisol concentrations were significantly higher at baseline in females, and increased more in response to stress, compared to males in both photoperiods. These results suggest that photoperiod provides a useful cue by which stressors in the environment may be anticipated in order to adjust immune function. Furthermore, interactions among reproductive status and stress responses appear to mediate the expression of sex differences in immune responses in hamsters.