Billy Hayes is caught attempting to smuggle drugs out of Turkey. The Turkish courts decide to make an example of him, sentencing him to more than 30 years in prison. Hayes has two opportunities for release: the appeals made by his lawyer, his family, and the American government, or the "Midnight Express".

Once again tampering with mother nature to disastrous results, Dr. Herbert West continues his research while serving time in a maximum security prison for his previous exploits. West's limited prison-cell experiments are suddenly interrupted by the arrival of a new prison doctor and the brother of the girl who suffered from West's experiments 13 years earlier.