It has been suggested that radicals on the surface of dust particles are key chemical factors in the pathophysiology that results from the occupational inhalation of coal and silica dust. In addition, oxygenated derivatives of arachidonic acid (eicosanoids) have been implicated as important biochemical mediators of mineral dust‐induced lung disease through their role in bronchial and vascular smooth muscle reactivity, inflammation, and fibrosis. Therefore, we assessed eicosanoid production by the rat alveolar macrophage (AM) exposed in vitro to mineral dusts with varying surface chemical characteristics in order to determine if radicals associated with the mineral dust could influence the production of proinflammatory mediators in the lung environment. Primary cultures of rat AM were exposed to freshly fractured or “stale” bituminous coal dust, as well as untreated silica or silica calcined to 500 and 1100°C. Prostaglandin E2(PGE2), thromboxane A2(TXA2), and leukotriene B4(LTB4) levels in incubation medium were determined by specific radioimmunoassay. When AM were exposed to freshly fractured coal dust, PGE2production was markedly increased. In contrast, exposure of AM to “stale” dust significantly reduced PGE2production. Exposure of AM to freshly fractured coal dust resulted in a significant increase in production by AM, while exposure to stale coal dust did not influence AM TXA2production. Neither “fresh” nor “stale” coal dust had any effect on LTB4production. In vitro exposure of AM to untreated silica resulted in a significant increase in TXA2PCE^ TXA2, and LTB4production compared with control. However, exposure of AM to silica calcined to 1100°C resulted in eicosanoid levels that were not significantly different from control. These effects were still apparent 8 wk after calcination of the silica particles. Silica was a more potent activator of AM eicosanoid production than was coal, and amorphous fumed silica was a more potent activator of AM eicosanoid production than was crystalline silica. These findings suggest that radicals associated with respirable coal and silica particles may play a key role in the ability of mineral dust to activate AM eicosanoid production and therefore may be important in the pathophysiological consequences of occupational mineral dust inhalation.