The effect of coal dusts containing ferrous-sulfate (7720787) (FeSO4) on the enzymatic activity of alpha-1-antitrypsin (alpha1- AT), a major serum inhibitor, was investigated, and the pulmonary response of guinea-pigs to carbon-black (1333864) or coal dust exposure was assessed. The coal dust samples used in this study were: Gardanne, Vouters, Mericourt, Escarpelles, La Mure, Illinois number 6, Bilson/Glen, Gealing, RME, UB, VI, DPQ, WGT, NS, JO, AH, and KLCFX. Reaction mixtures of coal dusts were prepared and subjected to a formate oxidation assay so as to measure oxidizing activity. Inactivation of alpha1-AT was measured by incubating the enzyme with aqueous filtrates of 100mg coal solutions and measuring the activity with a spectrophotometer. The dust exposure protocol involved subjecting male Hartley-guinea-pigs to 3 hour exposures of filtered air, pulverized Illinois number 6 coal, coal enriched with FeSO4, coal wetted in deionized water, coal washed twice with deionized water, carbon-black, or carbon enriched with FeSO4. At 24 hours postexposure, animals were sacrificed and bronchoalveolar lavage was performed. Supernatant was measured for total cell count, cell viability, total protein, and lactate-dehydrogenase. Macrophages were analyzed to measure phagocytic activity and reactive oxygen species. Results were manipulated via one way analysis of variance and Dunnett tests. The Vouters coal sample was active in both filtrate and aqueous coal suspension, and weak oxidizing activity was seen in coal samples from Escarpelles, Gealing, AH, and JO. The Vouters coal filtrate exhibited a dose dependent inhibition of alpha1-AT. No other tested coal filtrates exhibited any inhibitory effects on alpha1-AT. Coal enriched with FeSO4 caused a reduction in macrophage phagocytic activity. From this study the authors conclude that Fe(II) in coal dusts may contribute to coal dust induced lung disease, and that FeSO4 increases the pulmonary responsivity of guinea-pigs to coal dust exposure.