The maternal and developmental toxicity of combined exposure to restraint stress and caffeine was assessed in mice. On Day 9 of gestation, six groups of pregnant mice were treated (p.o.) with a single dose of 30, 60, or 120 mg/kg of caffeine. Immediately after caffeine administration, three of these groups were subjected to restraint for 14 hr. Control groups included unrestrained and restrained pregnant mice not exposed to caffeine. An additional group of animals (unrestrained and not exposed to caffeine) was deprived of food for 14 hr. A two-way (caffeine dose × restraint) analysis of variance revealed an overall effect (reduction) of restraint and caffeine exposure on maternal body weight gain and food consumption on gestation Days 9–11. Significant reductions were also observed in body weight at termination and corrected body weight change of dams concurrently exposed to 120 mg/kg of caffeine and restraint. By contrast, no significant effects of caffeine, restraint, or caffeine plus restraint on embryo/fetal development were noted. The doses of caffeine administered here are much higher than those usually consumed by the general population. Under the current experimental conditions, caffeine alone or combined with restraint stress was not embryotoxic or teratogenic in mice.