In the 1940s the author Patricia Highsmith, Picard's close friend, introduced her to the New York School and the Tenth Street galleries, where the perception that a work of art is a relic (or a record) of an act had begun to permeate the scene. By this time Picard had begun making collage- paintings and assemblages. Picard employed an orchestra of techniques obtained from the major movements of the European avant-garde. Like Kurt Schwitters, whom she recognized as a major influence, Picard collected rubbish from the streets and recycled her own trash and mementoes.

She embraced the theory that the object in the collage/assemblage pivots between what it was and what it represented. Picard frequently utilized wordplay in her works, a technique popularized by the Dadaists and surrealists in which multiple word definitions become part of the subject of the artwork. Subjecting her materials to messy and organic placement and manipulation, she exhibited a sense of the grotesque and tragicomic.

Picard's use of vivid colors may have been influenced by the painter Alfred Jensen, as well as Hans Hofmann, with whom both she and Jensen had studied. Picard was introduced to Jensen in 1952, and for more than ten years she was fascinated by both the man and his art. Jensen promoted a variety of ideas like Goethe's analysis of prismatic light, Mayan numeric and celestial systems, as well as various metaphysical and duality principles, which inspired Picard to explore their feasibility for her own work.

For example, in Collage in Blue, 1957, one of her first major works, two abstracted side-by-side figures seem to interact freely. The figure on the left can be identified as female, as the outline of a breast is suggested. The negative space serves to connect the figures in a kind of intercourse. A grid system of squares pulls the composition together.

In the late 1950s, Picard began to incorporate commercial cosmetics and beauty wares into her assemblages. 

Single and double (mirrored) female figures are comprised almost entirely of such manufactured objects as costume jewelry, curlers, hairpins, brushes, emery boards, rouge, and lipsticks-many with the tops off so that the red oily lipstick is revealed. The compositions are recognizable as figures-yet the cosmetic objects are placed with messy gobs of found string, fabric, metallic paper bits, torn and cut parts of product advertisements, even plastic soldiers and paint-usually white, although some of the pigment is red and green. White, red, and green would become Picard's most symbolic palette.

Engaged with the youth counterculture insofar as it was in rebellion against the conventions of mainstream U.S. society, Picard believed that art could maintain an individual's quest for "transcendence, self-actualization, and intimate community."

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