Research demonstrates that adolescents differ from adults in their response to drugs of abuse. The aim of the present study was to examine the influence of ethanol, Δ9-tetrahydrocannabinol hydrochloride (THC), and a combination of these drugs given during adolescence on spatial memory in adolescent and adult rats. Thus, adolescent rats (postnatal day (PND) 30) were subjected to the following groups: 0.9% NaCl; 1.5 g/kg ethanol; 1.0 mg/kg THC; 1.5 g/kg ethanol + 1.0 mg/kg THC. Rats received drug injection four times at three-day intervals. One day after the last injection, half of the treated animals were tested in the Barnes maze task, whereas the remaining animals were tested on PND 70. Results show that there was a significant age effect on spatial memory in the Barnes maze task after these drug administrations. Adolescent animals demonstrated more potent deficits in the spatial learning and memory (probe trial) and in cognitive flexibility (reversal learning) than did adults. However, in adult rats that received these drugs in adolescence, memory decline was observed only after ethanol and ethanol + THC administration. Thus, our results are important in understanding the deleterious impact of THC and/or ethanol abuse during adolescence on memory function across the lifespan (adolescent versus adult).