In 1487, the king of Spain, acting through Tomás de Torquemada, the first inquisitor general of the holy office of the Spanish inquisition, orders the first of the murders. For the next five centuries priests, cardinals, royal officials, nobles, and bankers are manipulated and killed by the guardians of the fourth angel to protect a secret plot and a vast and relentlessly growing fortune.

In the 21st century, Martín Ibarra Paz, a Cuban-American living in Miami, is famous for his work as the head of a team of architects designing and building a new capitol city in South America. Because his progenitors in Spain had been converted Jews, Martín becomes a target of the plot hatched by the reborn Spanish Inquisition.

Takeshi Ishikawa, the Brazilian-Japanese president of the newly-formed and tenuous Latino union, is desperate to keep the new union together and prevent South America from lapsing back into garrulous political divisions. His daughter, Gina Ishikawa, is a reporter covering the ascendance of the young new pope. She digs into his genealogy and finds he is not the man he claims to be.

A Vial Upon the Sun follows Gina as she teams with history professor Teodoro Lenin, television media technician Dennis Prinn, and revolutionary terrorist Nicolás Ibarra in a race across Latin America to save Martín and expose the New Inquisition to the world. Armed with nothing but their own knowledge, courage, and skills, they face paid assassins, a military coup, and a nuclear threat.

A Vial Upon the Sun is co-authored by father and son James Codlin and Craig Codlin.