Male CD-1 mice were daily exposed to handling stress from second to the nineteenth days of life. Eleven and 16 days after the interruption of stress, handled (HA) and control nonhandled (UHA) animals were tested to measure the baseline threshold for the perception of thermal nociceptive stimulation by the tail-flick test (TFT) and to assess the presence of the Straub tail response (STR). On day 50 of life, the antinociceptive response induced by intracerebroventricular B-endorphin (BE) was also studied. The results indicated that animals chronically handled during the neonatal period, at the age of 5 weeks, showed a strong activation of the endogenous opioid system as demonstrated by the higher response latency to the TFT, as well as by the presence of a marked STR. Then, at the age of 50 days, there was no longer a difference in the TFT latencies between UHA and HA groups, but a significantly reduced response to the antinociceptive effect of BE was present in HA mice.