Six months after intratracheal instillation of silica, histologic, ultrastructural, and cytologic studies were performed to characterize the inflammatory response in the lungs of guinea pigs. Granulomatous and diffuse interstitial infiltration occurred predominantly in the peribronchial regions. Ultrastructural evaluation confirmed the presence of a mixed cellular infiltrate and fibrosis in the alveolar interstitium and Type II lining cell hyperplasia. Recovery of bronchoalveolar cells by whole lung lavage and the proportion of neutrophils and multinucleated giant cells in this population were significantly higher in experimental animals (p < 0.05) than in controls (intratracheal saline). Lung macrophages from experimental animals exhibited impaired adherence and motility in vitro. The mechanisms by which inflammatory cells might be recruited into the lungs of these animals and the importance of altered macrophage function are discussed.