Two American couples, Jeff and Amy and Eric and Stacy, are on holiday in Mexico. At their resort, they meet Mathias, a German tourist whose brother Heinrich went off to an archaeological dig at a remote Mayan ruin and has not come back. Mathias plans to go find him, and the friends decide to come along, together with Dimitri, a Greek tourist from the resort.

After a long walk through the jungle, they find a huge stone temple covered in green vines with red flowers. Within moments, a group of Mayan villagers arrive on horseback with guns and bows, shouting at them. When Amy steps back onto the vines, the villagers become even more angry. Dimitri tries to calm them, and they shoot and kill him. The others run up the steps of the temple, and the villagers surround it and refuse to let them come down.

At the top they find Heinrich's empty camp and a deep shaft going down into the temple. They hear a phone ringing at the bottom and think it might be a survivor. They lower Mathias down on a rope, but it breaks, and he falls and breaks his back. Amy and Stacy climb down to bring him back up. In anger, Amy throws vines at a young village boy, and the villagers kill the boy on the spot. The friends realize the truth: the villagers are not keeping them prisoner out of cruelty. Anyone who touches the vines is never allowed to leave, so the plant can never spread.

The vines turn out to be alive and hungry. They creep into open wounds, eat flesh, and copy sounds, like a ringing phone and human voices. At night they eat through Mathias's legs down to the bone, so Jeff, who is about to start medical school, cuts both legs off to try to save him. It does not work, and the vines later strangle him. Stacy finds vines growing in a cut on her leg, and Jeff has to cut them out. Without food or clean water, the group starts to fall apart.

Stacy becomes sure the vines are still growing inside her, and she is right. She starts cutting herself open with a knife to dig them out. When Jeff tries to stop her, she cuts his hand, and when Eric tries, she stabs him in the chest, and he dies. The vines drag his body away. Broken and in pain, Stacy begs them to end her suffering, and Jeff kills her out of mercy.

Jeff then comes up with a plan to save Amy. He covers her in Stacy's blood so she looks dead and carries her down the temple steps. While he distracts the villagers by shouting and walking toward them, Amy runs for the jungle. The lead villager shoots Jeff dead. Amy reaches a Jeep and drives away, the only one who escapes. In the last scene, two of Dimitri's Greek friends arrive at the temple looking for him, so the cycle is about to start again.

So is Amy free? In the theatrical cut, the answer is left open. In the unrated version, the camera moves in on Amy's face as she drives away and shows vines moving under her skin, which means she is carrying the plant out into the world. That is exactly what the villagers were trying to stop. A deleted extended ending takes it further, with red flowers blooming around Amy's grave. The film never explains where the vine came from. It simply suggests the villagers have been guarding it for a long time, and that they are the only thing keeping it from spreading.