Short days inhibit reproduction and enhance immune function in deer mice (Peromyscus maniculatus). Their reproductive inhibition is sustained by an endogenous timing mechanism: after ca. 20 weeks in short days, reproductive photorefractoriness develops, followed by spontaneous recrudescence of the reproductive system. It is unknown whether analogous seasonal timing mechanisms regulate their immune function or whether enhanced immune function is sustained indefinitely under short days. In order to test this hypothesis, we housed adult male deer mice under long (16 h light day(-1)) or short (8 h light day(-1)) day conditions for 32 weeks or under long day conditions for 20 weeks followed by 12 weeks of short days. Mice under the long day conditions remained photostimulated over the 32 weeks, whereas mice housed under the short day conditions exhibited gonadal regression followed by photorefractoriness and spontaneous recrudescence. Mice transferred to short days at week 20 were reproductively photoregressed at week 32. Total splenocytes, relative splenic mass and mitogen-activated splenocyte proliferation were greater in those mice transferred to short days at week 20 than in those mice housed under either long or short day conditions for 32 consecutive weeks, and immune function in mice exposed to short days for 32 weeks was comparable with that of long day animals. These data suggest that short day enhancement of immune function is not indefinite. With prolonged (< or = 32 weeks) exposure to short days, several measures of immune function exhibit "spontaneous" regression, restoring long day-like immunocompetence. The results suggest that formal similarities and, possibly, common substrates exist among the photoperiodic timekeeping mechanisms that regulate seasonal transitions in reproductive and immune function.