A defect of cell-mediated immunity was reported in patients with Crohn's disease. In attempting to evaluate the possible role of serum factor(s) in the pathogenesis of this defect we studied the effect of sera from patients with Crohn's disease on normal lymphocyte E rosette formation and in vitro PHA responsiveness. An impairment of E rosette formation and PHA response was detected when normal donor lymphocytes were incubated with patients' sera. We concluded that the defect of cell-mediated immunity in Crohn's disease may be due to the presence of serum inhibitory factor(s) and of nutrient serum deficiencies. This defect is not correlated with clinical parameters and the duration of the disease; it is not affected by surgical resection.