Peripheral blood leukocytes from 12 patients with progressive systemic sclerosis and from 12 normal subjects were cultured in the presence of human skin collagen, lathryritic chick skin collagen, and alpha-chains from chick skin collagen. Leukocytes from 11 of the patients produced a factor chemotactic for human monocytes when cultured with the collagen preparations. The one patient whose cells did not respond to the collagen preparations also failed to respond to other common antigens and was apparently anergic. In addition, lymphocytes from three of the patients were found to transform when cultured with the collagen preparations. These responses were significantly different from the response of leukocytes from normal control subjects. The data suggest that patients with progressive systemic sclerosis may have cellular immunity to collagen.