The etiology of Crohn's disease is still unknown. The present study served to test the hypothesis that baker's yeast (Saccharomyces cerevisiae) plays a role in Crohn's disease. Blood samples were obtained from 12 patients and 15 healthy controls. Peripheral blood leukocytes were isolated and incubated alone or with different concentrations of baker's yeast. After 3 days, the cultures were pulsed with tritiated thymidine. None of the lymphocyte cultures from healthy controls, including 3 bakers, proliferated in response to yeast. In striking contrast, all 9 patients with Crohn's disease in remission, on no medication, showed a threefold increase in their lymphocyte proliferation rate. Lymphocytes from 3 patients on 1.5 g of olsalazine maintenance therapy failed to respond. These results are consistent with previous findings that showed increased titers of IgG and IgA antibodies to baker's yeast in patients with Crohn's disease as compared to healthy controls. They confirm the suspicion that baker's yeast itself or a related antigen play a role in Crohn's disease and suggest that anti-inflammatory agents may act, in part, by inhibiting lymphocyte proliferation.