A metal-segregated layered compound, containing square nets of Cu(pyz)(2)(2+) and buckled V6O162- layers, has been synthesized using hydrothermal techniques to have the composition V6O16Cu-(C4H4N2)(2).(H2O)(0.22(1)) AHA pyrazine, pyz). The Cu(II) square nets are nearly regular and undergo an antiferromagnetic transition at 8 K. In contrast to the plethora of recently synthesized metaloxide clusters, chains, and networks in the VOx/M/L (M = late transition element; L = organonitrogen ligand) system, this compound is a relatively rare example that contains two different metals distributed into distinct layers. An application of charge density matching to form layered structures is postulated.