Antigen preparations derived from Plasmodium falciparum-infected erythrocytes (but not from uninfected erythrocytes) can stimulate the in vitro proliferation of peripheral blood lymphocytes from malaria-sensitized as well as nonsensitized donors. The possibility that the nonspecific responses might be due to a parasite-derived B-cell mitogen has been previously suggested since polyclonal hypergammaglobulinemia is a frequent accompaniment of malaria infection. To test this hypothesis, we investigated the in vitro proliferative responses of purified T- and B-cell populations to malaria antigens. T but not B cells responded to the antigens. The addition of small numbers of T cells restored the ability of purified B cells to respond to lectin mitogens but not to malaria antigens. Falciparum malaria infection was associated with an increase in T-cell but not in B-cell proliferation in vivo, as assessed by the spontaneous tritiated thymidine incorporation of lymphocytes during a brief incubation in vitro. Our observations suggest that extracts of malaria parasites do not contain a B-cell mitogen but are antigenic as well as mitogenic for T cells.