The peripheral blood lymphocyte response to affinity purified soluble Plasmodium falciparum antigens from in vitro cultures was studied in seven patients with acute falciparum malaria, on eight occasions, and in 15 persons having had malaria, at various times post infection, on 24 occasions. During infection, the response was low or absent in most patients (median stimulating index = [SI] = 1.4). One week post infection, a specific antigen response rose (SI = 2.9), but not to the levels found two weeks to one year post infection (SI = 5.8). At two to four years post infection, it was still present. During a recrudescence of malaria in a single patient, it was lost temporarily. The response to optimal concentrations of lectin mitogens and to tuberculin antigen was not suppressed in acute malaria.