Insult to the germ cells of an ovum or sperm prior to pregnancy as well as exposures to a fetus during pregnancy can affect the outcome of a pregnancy. Antineoplastic agents are mutagenic and teratogenic, so the potential effects of exposure on reproduction are of concern to the workers who handle them. This study investigates pregnancy loss associated with occupational exposures to antineoplastic drugs by comparing rates of spontaneous abortion and stillbirths for pregnancies without antineoplastic exposure and exposed pregnancies in which the pregnant woman or the father handled antineoplastic agents either before or during the pregnancy. A total of 7094 pregnancies of 2976 pharmacy and nursing staff were examined. After age during pregnancy, prior gravidity, maternal smoking during the pregnancy, and occurrence of a spontaneous abortion or stillbirth in a prior pregnancy were controlled for, exposure of the mother to or the handling of antineoplastic agents during the pregnancy was associated with a significantly increased risk of spontaneous abortion (odds ratio = 1.5; 95% confidence interval, 1.2 to 1.8) and combined risk of spontaneous abortion and stillbirth (odds ratio = 1.4; 95% confidence interval, 1.2 to 1.7) but not stillbirth alone. Among the wives of exposed men, too few stillbirths occurred to allow analysis. However, for spontaneous abortion and any loss, the patterns of increased risk were similar to those seen for women, although the odds ratios were not statistically significant.