Plasma collected from owl monkeys during the acute phase of Plasmodium falciparum infection was shown to adversely affect several in vitro responses which are considered to be correlates of cell-mediated immune functions of normal monkeys. In the presence of acute-phase plasma, response of normal monkey peripheral blood lymphocytes to stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen was severely reduced, as was the ability of peripheral blood lymphocytes to respond to allogenic and xenogenic histocompatible antigens. The transformation response of peripheral blood lymphocytes from normal humans to phytohemagglutinin and concanavalin A was also suppressed. Since acute-phase plasma was not cytotoxic for peripheral blood lymphocytes, decreased responsiveness did not result from cell destruction. Acute-phase plasma appears to block initial steps in lymphocyte transformation.