The effect of Entamoeba histolytica extracts (E.h.e.) on proliferation in vitro of human peripheral blood lymphocytes, cord blood lymphocytes, and lymphocytes enriched for T cells or non-T cells was investigated. As tested by 3H-thymidine uptake and by morphologic criteria, E.h.e. stimulate T lymphocyte proliferation. Non-T lymphocytes do not respond to E.h.e. The response of lymphocytes to E.h.e. differed from their response to Con A in several respects, indicating either that E.h.e. and Con A act on different subsets of T cells or that E.h.e. act by different mechanism on the Con A reactive cells.