Artists from different parts of Italy approached the representation of nature differently and, as a result, produced works that differ not only in execution and appearance but in their very conception. In Florence, disegno, that is, "drawing" or "design," was viewed as the essential beginning of artistic endeavor, the primary means for making art approximate nature. In Venice, colorito, "coloring"—not only color but also its judicious application—was deemed fundamental to conceiving painted images charged with the look of life. Florentine color was frequently more vivid than the palette used in Venetian paintings; typically Venetian, however, was the process of layering and blending colors to achieve a glowing richness. A long-lived debate between the two positions involved theorists as well as artists and regional rivalries as well as aesthetic concerns.

Giorgio Vasari, a Florentine artist and writer, described disegno as the father and foundation of all the visual arts, "the animating principle of all creative processes." For the Florentines and other Central Italian artists, the act of drawing was not only the art of using line to define form: it was the artistic underpinning of a work whereby an artist could express his inner vision. Florentine painters therefore used drawing to study movement, anatomy, and the natural world, and they developed compositions in detailed drawings before transferring them to surfaces prepared for painting. In a late fifteenth-century drawing by Filippino Lippi (Standing Youth, 36.101.1), for example, the artist uses hatched shading and careful contours to describe volume and movement in two artfully posed figures. On another sheet, Michelangelo plans a sibyl for the Sistine Chapel ceiling in red-chalk strokes remarkable for their consistency and power (24.197.2, recto). Although painted in different media, such Florentine paintings as Ghirlandaio's fresco of Saint Christopher (80.3.674) and Bronzino's oil on panel Portrait of a Young Man (29.100.16) share hard contours and a sculptural quality, an effect resulting from the detailed preparatory drawings required by Florentine working practice.

According to Vasari, Tuscan artists revived disegno and art was reborn; according to Lodovico Dolce, Venetian artists gradually softened their coloring until their manner equaled nature. Rather than beginning with careful drawings, Venetian painters often worked out compositions directly on the canvas, using layered patches of colored brushstrokes rather than line to define form. Venetian drawings show an interest in how light will affect a body and how color will describe it in a painting. In Vittore Carpaccio's sheet of studies of a seated youth in armor (54.119), for example, highlight and shadow applied with a brush represent the sheen of metal and the forms of the young man's face. Titian's painting of Venus and Adonis (49.7.16) shows similar sensibilities: a mass of golden touches represents the pearls and highlights in the goddess's blond hair, and the subtle modulations of tone across her back suggest flesh without sharp edges. In his dialogue on painting, Dolce champions Titian for his naturalism over Michelangelo, Vasari's hero. In a similar spirit, the Venetian painter Tintoretto confronts the Florentine achievement in a drawing after Day a marble sculpture by Michelangelo (Reclining Figure of Day, 54.125). The broken contours and painterly handling of the highlights in the drawing seem to answer the taut and stony design of Michelangelo with the subtle richness of Venetian coloring.