Risk of spontaneous abortion (SAB) was examined in relation to chemical and physical agents in a retrospective study of employees of 14 seminconductor manufacturers: After screening over 6,000 employees, 506 current and 385 former workers were eligible. If a woman had multiple eligible pregnancies, one was selected at random. Telephone interviews provided data on demographics and occupational and other exposures during the first trimester. Two groups of chemicals accounted for the 45% excess risk of SAB among fabrication-room (fab) workers: photoresist and developed solvents (PDS), including glycol ethers, and fluoride compounds used in etching. Women exposed to high levels of both these agents were at greater risk (RR = 3.21, 95% confidence interval [CI] = 1.29-5.96). In fab workers without these exposures, SAB rates were not elevated (adjusted relative risk [RR] = 0.98, 95% CI = 0.55-1.69). An association was seen with workplace stress, which was not limited to women exposed to PDS or fluoride, nor did stress explain the associations between these chemicals and SAB.