Human colostrum contains a factor that inhibits the induction of interleukin 2 (IL2) in T lymphocyte cell lines (colostrum inhibitory factor, CIF). In PMA-stimulated EL4.E1 cells, inhibition is the result of blocking the accumulation of IL2 mRNA. Human colostrum contains on the order of 100 U/ml of CIF activity, where 1 U/ml inhibits 50% of the IL2 response. Transient acidification to pH 3.0 increased CIF activity severalfold. Although it resembles TGF beta in some respects, antisera against TGF beta neutralized 10% or less of the CIF activity in human colostrum. Furthermore, whereas authentic TGF beta blocked the induction of IL2 by PMA-plus-calcium-stimulated cells by only about 50%, CIF inhibited it completely. A similar CIF activity was also detected in bovine colostrum, but not in normal bovine milk.