Antigen-specific human T lymphocytes were selected by adsorption of peripheral blood mononuclear cells on monolayers of antigen-treated autologous monocytes. The enriched cell populations were propagated in interleukin 2-containing medium for 60-80 days. Their activity was tested by a proliferative response against the sensitizing antigen in the presence of irradiated autologous lymphocytes. Continuous cultures of enriched T cells responded specifically to three different protein antigens. The specific reactivity induced in vitro against at least one of the antigens was probably a primary response. In addition, the selected cultures were found to be enriched for OKT4-positive cells, in contrast to cultures of nonselected T cells which were enriched for OKT8-positive cells. These properties of the selected T lymphocyte populations were obtained following only one exposure to the sensitizing antigen, which was concomitant with adsorbance on monocytes and without cloning of the reactive cells. We suggest that specific adsorbance of lymphocytes on antigen-treated monocytes may result in a T cell population which combines both properties of antigen specificity and enrichment for the helper proliferative subset of T cells.