Mixed lymphocyte culture reactions between maternal and related neonatal cells at delivery, and maternal and paternal cells about a week after delivery, and the effect of maternal serum and HLA antigens on these reactions were studied in 11 families with primiparous or secundiparous mothers and in 13 families with multiparous mothers (six or more pregnancies). Weak or absent MLC response of the mother to her infant was observed in one-third of primiparous and secundiparous mothers and in one-half of multiparous mothers. In some cases the non-reactivity could be due to genetic similarity, i.e. HLA or HLA-D identity between the mother and her infant. In other cases, this was obviously not a valid explanation and no apparent reason for the non-reactivity was found. The MLC suppressing effect of maternal serum on MLC reactions at delivery and about a week later was not correlated with the strength of maternal-neonatal MLC reaction. Four of the ten sera from multiparous mothers studied a week after delivery had an inhibitory effect of 50% or more on MLC reactions involving stimulatory paternal cells. Responding paternal cells and other MLC combinations were also inhibited to varying degrees. None of the sera of primiparous and secundiparous mothers had an equally strong MLC inhibiting effect.