Soluble exoantigens of Trypanosoma lewisi were obtained from short-culture systems of dividing epimastigotes and non-dividing trypomastigotes incubated in phosphate-buffered saline glucose solution (PBSG) for 3 h at 37 degrees C. Suppression of normal rat-spleen cell responses to mitogen concanavalin A (Con A) occurred at high exoantigens concentrations. The epimastigote-derived exoantigens were more suppressive than the trypomastigote-derived exoantigens. The suppression of Con A stimulation was ablated by the addition of exogenous interleukin-2 (IL-2) or washing of spleen cells that had been incubated with suppressing concentrations of the epimastigote exoantigens for 24 h prior to Con A stimulation. These results strongly suggest that exoantigens of T. lewisi play an important immunoregulatory role during the course of infection and that they achieve this by inhibiting the production of IL-2 by T-helper cells.