Nontropical rodents often experience large seasonal fluctuations in both food availability and energy demands. The energy required for thermoregulation is highest during the winter when food availability may be at an annual minimum. Failure to cope with winter probably accounts, in part, for the increased prevalence of disease and death relative to that in summer. Winter conditions may elevate circulating glucocorticosteroid levels, which can compromise immune function. To increase the odds of surviving the energetic demands of winter, individuals of some rodent species appear to enhance immune function before conditions deteriorate. Previous laboratory studies suggest that immune enhancement can be induced by short days. These findings contrast with the results of several field studies reporting suppressed immune function during the winter. To resolve this conflict, the authors hypothesized that winter stressors present in field studies counteracted the short-day enhancement of immune function reported in laboratory studies. If true, then immune function of captive mice in short days should be compromised by low temperature or reduced food availability. Both ambient temperature and photoperiod were manipulated in the present study to assess their effects on immune parameters in male deer mice (Peromyscus maniculatus). Animals in short days regressed their reproductive systems and also displayed significantly higher immunoglobulin G (IgG) levels than did those in long days. Deer mice maintained in low temperatures had significantly reduced splenic masses and basal IgG levels independent of day length. Animals maintained in both short days and low temperatures displayed IgG levels comparable to those of mice in long-day/mild-temperature conditions. Animals maintained in long days and low temperatures had significantly higher serum corticosterone levels than did animals maintained in long days at mild temperatures. These data are consistent with the hypothesis that immune parameters are enhanced in short days to counteract stress-mediated immune suppression occurring during the winter.