This study tested the hypothesis that fabrication room (fab) work in the silicon-based semiconductor industry is associated with an increased risk of spontaneous abortion (SAB). The study was conducted nationwide at 14 companies representing a spectrum of large to small manufacturers. A small increase in risk of SAB was observed among fab workers compared with nonfabrication room (nonfab) workers in two cohorts, historical (adjusted RR = 1.43, 95% confidence interval [CI] 0.95-2.09) and prospective (adjusted RR = 1.25, 95% CI = 0.63-1.76). Analysis of specific fab exposures in the historical cohort showed a consistent, dose-response association of SAB with photoresist and developer solvents, whose major component was ethylene-based glycol ethers. The consistency of our findings and the toxicological data for these agents suggest that this is a causal association. Independent associations of SAB with self-reported stress and with etching fluorides were observed and require further research. No significant decrease in fertility was observed among men or women working in fabs, but reduced fecundability was suggested for some women fab workers.