Rats, guinea pigs, and monkeys were exposed by inhalation (5.5 to 6 h/day, 5 days/week) for up to 18 months at 15 mg/m³ concentrations of three types of synthetic amorphous silicas: fume, gel, and precipitated. Autopsies on rats were performed after 3, 6, and 12 months of exposure, and on guinea pigs and monkeys after 10 to 18 months of exposure. The most significant finding was the deposition of large quantities of amorphous silica in macrophages in the lungs and tracheal lymph nodes of exposed monkeys. Relatively few or no macrophages containing particles of amorphous silica were found in the lungs and lymph nodes of the guinea pigs and rats. It is also significant that fume silica induced early nodular fibrosis in the lungs of the monkeys. Correlating these histological findings, lung-function studies indicated statistically significant differences in lung volume and ventilatory mechanics measurements between those monkeys exposed to fume silica and the control group. In addition, monkeys exposed to precipitated silica demonstrated significantly lower lung volumes compared with controls, while monkeys exposed to silica gel had significant changes in ventilatory performance and mechanical properties.