New York City women (321) enrolled during 1986-1993 in an observational cohort study were analyzed retrospectively to determine the effectiveness of antenatal zidovudine in reducing perinatal transmission of human immunodeficiency virus type 1 (HIV-1) in women with various CD4+ lymphocyte counts (< 200, 200-499, > 499/microL). When CD4+ lymphocyte level was controlled for, women prescribed zidovudine during pregnancy were less likely to transmit HIV-1 to their infants (adjusted odds ratio, 0.36; 95% confidence interval, 0.14-0.92). There was no conclusive evidence that efficacy of zidovudine depended on CD4+ lymphocyte level, suggesting that women with severe CD4+ cell depression, who are at highest risk of transmitting HIV-1, may also benefit from zidovudine. Antenatal zidovudine treatment alone may substantially lower the risk of perinatal HIV-1 transmission. These data are consistent with the results of AIDS Clinical Trial Group protocol 076 and suggest that a substantial portion of zidovudine's protective effect may occur when used during the antenatal period.