A firearm with tilting barrel-receiver assembly includes a frame and a barrel-receiver assembly pivotably mounted to the frame. The barrel-receiver assembly is movable between an open position and a closed position. A latching mechanism includes a latch that selectively engages the barrel-receiver assembly. The latching mechanism may be disposed in the frame in one embodiment. The latching mechanism is movable between a locked position wherein the barrel-receiver assembly is held in the closed position and an unlocked position wherein the barrel-receiver assembly is movable to the tilted open position. The latch may be spring biased into the locked position. The barrel-receiver assembly may be configured for complete removal from the pistol in some embodiments. An interlock mechanism formed by a movable safety may be provided which prevents the barrel-receiver assembly from being unlocked when the firearm is in a ready-to-fire condition.