Experiments were conducted to ascertain to what extent the mitogen response of human peripheral T cells is influenced by contaminated, nonresponding leukocytes. T- and B-lymphocyte preparations, extensively depleted of monocytes, exhibited extremely poor responses to pokeweed mitogen and concanavalin A compared with the original unfractionated cell population. A strongly reduced phytohemagglutinin response was noted in the B-cell but not in the T-cell fraction. Mixtures of cell preparations enriched in T or B cells yielded stimulations higher than expected. Mitomycin-C-treated T-cell preparations mixed with untreated preparations enriched in B cells gave slightly higher responses than expected. However, highly enhanced responses were observed when untreated T cells were mixed with mitomycin-treated cell suspensions enriched in B cells. A similar enhancing effect was noted when mitomycin-treated cell suspensions enriched in adherent cells were added. It is concluded that the mitogen reactivity of T cells, on a cell-for-cell basis, may be enhanced tenfold or more by cocultivation with unresponsive non-T leukocytes. A reduced mitogen reactivity of peripheral lymphoid cells from patients with various types of disease may thus either reflect a decreased proportion of responsive lymphocytes or unresponsive non-T lymphocytes capable of enhancing mitogen reactivity, or both.