To examine the perinatal effects of caffeine on pup behavior and brain neurochemistry, rat mothers were exposed to caffeine in a choice situation prenatally, postnatally, at both times or at neither time. Prenatally, caffeine-exposed mothers drank approximately 14 mg/kg/day, an amount ineffective in altering mothers' overall prenatal body weight, although it did reliably decrease birth femur length of offspring. Postnatal pup activity measures revealed that postnatal caffeine exposure depressed activity, with an additional contribution of prenatal caffeine exposure. Those effects occurred at caffeine intake levels (circa 48 mg/kg/day) which minimally affected pup body weight, body length, femur length or eye-opening. Postwithdrawal (35 days of age) biochemical determinations revealed significant postnatal effects of caffeine by depressing cyclic AMP/"whole-brain" and elevating the cyclic GMP/cyclic AMP ratio in cerebellum. Whole-brain levels of dopamine and norepinephrine, however, were not affected by the caffeine treatments. These results suggest that activity profiles may be a more sensitive index of caffeine "toxicity" than other indices of physical development, and that cyclic nucleotides may play at least some role in the hypoactivity-inducing effects of caffeine in developing rats.