Lymphocytes of 628 pregnant women were tested for natural cytotoxic activity to human embryonic fibroblast cells. The data were analyzed with regard to previous obstetric history, symptoms occurring during the present gestation, and the outcome of pregnancy. The normal rate of cytotoxicity during pregnancy was established by determining cytotoxic activity of the lymphocytes from 56 healthy pregnant women. The values higher than the mean + 2 SD of the "normal" (greater than or equal to 40%) were considered as high. Increased cytotoxicity was associated with the occurrence of previous spontaneous and missed abortions, as well as with bleeding and uterine contractions during the present pregnancy observed at the time of the test. In 15 out of 35 cases resulting in spontaneous abortion and 15 out of the 34 pregnancies resulting in missed abortion, cytotoxic activity of the lymphocytes during pregnancy was higher than normal. Similarly, in 38 and 32.7% of the pregnancies resulting in preterm (n = 121) or low birth-weight deliveries (n = 101) respectively, we found increased lymphocyte cytotoxicity, in contrast to that being found in 5.4% of uncomplicated normal pregnancies. These data suggest that at least some pregnancy failures might be immunologically mediated.