We conducted a case-control study of spontaneous abortion in Santa Clara County, California between 1986 and 1987. We analyzed data on 607 cases and 1,284 controls to evaluate the potential association between caffeine consumption during the first trimester of pregnancy and spontaneous abortion. About 70% of the women consumed caffeinated coffee, tea, and/or soda; 7% of the women consumed more than an average of 300 mg of caffeine daily. The crude odds ratio (OR) for heavy caffeine consumption (greater than 300 mg/day) was 1.55 (95% CI: 1.04-2.31), which decreased to 1.22 (95% CI: 0.80-1.87) after controlling for confounding factors. For these heavy users, nausea modified the association of spontaneous abortion and caffeine; heavy caffeine consumers reporting nausea had a doubled risk for spontaneous abortion (adjusted OR = 2.10, 95% CI: 1.20-3.70), in contrast to those who did not report nausea (adjusted OR = 0.53, 95% CI: 0.27-1.04). Heavy caffeine consumers who decreased their caffeine intake early in pregnancy had a risk of spontaneous abortion similar to that of nonconsumers.