Twenty-four cases of pulmonary alveolar proteinosis (PAP) were studied by light microscopy (LM) and scanning electron microscopy (SEM) to test the hypothesis that PAP was related to silica exposure. Increased numbers of birefringent particles (vs. controls) were found in 78% of PAP cases. SEM was used to locate inorganic particulates in situ, which were individually analyzed using energy dispersive X-ray analysis. When analyzed as an aggregate group of cases, no specific inorganic particulate was evidently associated with the PAP reaction. However, analysis of individual cases revealed more specific associations. The concentration of particles determined by SEM exceeded that found by LM by a factor ranging from 2.7 to 964. The concentration of inorganic particulates per cm3 in the areas of PAP ranged from 1.3 X 10(7) to 1.02 X 10(9). Controls all had less than 10(7) particles per cm3. Available environmental history correlated well with particulate analysis results, e.g., silica in a sandblaster, metal fumes in a welder, and cement particles in a cement finisher. Particulates with unique composition were also found in cases with unavailable histories, e.g. metal fumes suggestive of welding or soldering exposure, silicates suggestive of fine particle exposure (greater than 50% of particles less than 1 micron). Only 1 case (the sandblaster) showed greater than 50% of the particles to be silica. Of the 5 infants with PAP, 3 showed the major particulate to be talc, and 1 had evidence of toxic cadmium selenide fume exposure. These results are consistent with the hypothesis that PAP, at least in the majority of cases, is associated with exposure to small inorganic particulates of several types.