Although the use of chloroquine (C) and hydroxychloroquine (HC) in the treatment of malaria prophylaxis during pregnancy is probably safe, the use of much higher doses for treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis during pregnancy has been controversial. We analyzed the cases of 24 pregnant women with a total of 27 pregnancies who had taken these drugs during their first trimester of pregnancy. C and HC were given in 11 patients with SLE, three with rheumatoid arthritis, and four for malaria prophylaxis. Most of these women had already been on antimalarial drugs for 1 to 172 months prior to pregnancy (mean, 32.2 months). Of the 27 pregnancies, 14 resulted in normal full-term deliveries, six were aborted due to severe disease activity or social conditions, three were stillbirths, and four pregnancies resulted in spontaneous abortions. No congenital abnormalities were detected in the 14 live births at ages between 9 months and 19 years (mean, 5.3 years). All these children are physically and developmentally normal with no clinical evidence of eye or hearing defects. The seven pregnancies that were associated with fetal loss occurred particularly in patients who had active SLE, although stillbirth and spontaneous abortion occurred also in patients with rheumatoid arthritis and in two of the three patients who had been treated prophylactically for malaria. Although of the 215 reported pregnancies with C and HC exposure, including our study, only seven (3.3%) had congenital abnormalities, the risk associated with antimalarials may be cumulative and further studies are needed to elucidate the safety of this drug later in pregnancy.