In 1595, Annibale entered the service of Cardinal Odoardo Farnese in Rome, and it was he who was responsible for exporting to the first city of Christendom the Carracci's reformed style of painting, which Annibale continued to develop with reference to the canonical Roman models of an idealized ancient and Renaissance art. Annibale remained with Cardinal Farnese for ten years, producing his greatest work, the frescoes in the gallery of the Palazzo Farnese, between 1597 and 1601. In 1605, he suffered a nearly complete mental breakdown, and four years later he died miserably, but not before having developed - with the help of his students - a final synthesis of warm, naturalistic Northern color and light with a highly abstract and classical formal vocabulary.

It was Caravaggio, already in Rome when Annibale first arrived there, who first grasped the full illusionistic potential of Bolognese techniques of handling color and light. Both Caravaggio and Annibale were perceived in the seventeenth century as exponents of a North Italian or "Lombard" tradition of naturalism that was opposed to the excessive aestheticism of Mannerist practice then prevalent in Rome, Even before Annibale came to the city, Caravaggio's style was recognized as a product of the naturalistic conventions of the Veneto-Lombard culture in which he had been raised; the full power of Caravaggio's mature style emerged after Annibale's arrival in Rome - first in the Contarelli Chapel, and then in his definitive statement, the Cerasi Chapel, where Annibale painted the altarpiece. The effect of Caravaggio's work was shocking, as we know from the rejection of his original version of the Conversion of Saint Paul, and it was at once apparent that the naturalistic illusionism of Lombardy, even though anti-Mannerist, had produced sharply divergent tendencies - tendencies that stood in a dialectically polemical relationship. Already in 1603, van Mander reports that Caravaggio scorned the principle of artistic selection, with its goal of realizing a perfected ideal of nature, insisting upon absolute faith to the individual model, depicting the truth of particular experience. Annibale, on the other hand, sought to give naturalistic verisimilitude to a perfected ideal that was deducible from experience, to represent not what is but what might be and what ought to be, and, in so doing, to inspire the viewer to virtue. His altarpiece for the Cerasi Chapel, in contrast to Caravaggio's two paintings on the side walls, emphasizes in the strongest possible way the divergence between the two artists' conceptions of the problem of reality. They are strictly antithetical, and were immediately understood to be so by their contemporaries. In that antithesis - not in the opposition of naturalism to Mannerism - appears the fundamental problem of Counter-Reformation culture.