Aged individuals exhibit an impairment of T helper and/or T suppressor activity on B cell function in an antibody-specific induction system. Further evidence is now provided that soluble suppressive factors acting on monocytes play a key role in such deficits. In fact, overnight preincubation of isolated monocytes and supplementation of autologous lymphocytes reverses the immunoregulatory imbalance. The suppressive factors are also responsible for a decreased interleukin 2 (IL-2) synthesis since a similar pretreatment of cell suspensions or exogenous human IL-1 and/or IL-2 supplementation of aged cell cultures leads to a recovery of T regulatory effects on B cell differentiation. Similar effects are observed in the presence of thymopentin, a well known IL-2 inducer. Interferon alpha and gamma addition to cultures gives rise to a restoration of T immunoregulatory effects. These findings suggest that several mechanisms are involved in the depressed T immunoregulatory activity in the elderly.