381 Lafayette Street, date unknown.

The original address of 381 Lafayette Street was 6 Lafayette Place (prior to the street being renamed in the early 20th century). The four-story, red brick building was the residence of wealthy merchant Alexander Mactier in 1939. Later the home, which once had a tall stoop, was owned by a well-known and respected surgeon, Dr. Alexander H. Stevens. As the neighborhood developed into a commercial area, the residents left and the buildings were converted into places of business. In the 1860s a Madame Ferrero sold fancy French and Italian hats to New York's wealthy ladies, and later the building was a doctor's office as well. In 1888 it was sold to The Mission of the Immaculate Virgin for the Protection of Homeless and Destitute Children. That organization erected a large neighboring residential hall at nos. 2 and 4 Lafayette Place, while no. 6 became the convent and chapel for the nuns who operated the mission home. The building underwent a renovation in 1890, adding two stories, a rear extension, and a new Northern Renaissance Revival style facade.

By 1930 the large mission residence was being demolished after a decade of vacancy when most of the charity's functions were moved to Staten Island. The convent building, by now numbered 381 Lafayette Street, remained owned and used by the mission until 1965. The painted sign on the side of the building relates to its work with homeless children. The building was sold and resold in the 1960s, finally to the artist Robert Rauschenberg. No. 381 became his studio and home until his death in 2008. Today the building (which underwent a facade restoration in 2008) remains the home of the Robert Rauschenberg Foundation.