Mononuclear cells from twenty-one patients with depressed cellular reactivity were assessed for the ability to produce leucocyte inhibitory factor (LIF) and to transform after PHA stimulation, in the presence or absence of levamisole. Cells from nineteen patients failed to produce significant lymphokines when stimulated with PHA alone, but after a prior 1-hr levamisole pulse normal amounts of LIF were produced. Unstimulated mononuclear cell supernatants from six patients showed LIF-like activity, which could be abolished or decreased in five of the six when the cells were initially treated with levamisole. Mononuclear cells from seven of twelve patients which failed to incorporate [3H]thymidine after PHA activation, showed an increased response after a 1-hr levamisole pulse. Unstimulated mononuclear supernatants from six patients inhibited the lymphoproliferative response of normal cells to PHA. After treatment with levamisole, however, the suppressive effect of these supernatants was decreased or abolished. In vitro levamisole treatment, therefore, not only restores cellular responsiveness in anergic patients but also restricts the uncontrolled release of inhibitory factors.