In vitro interaction of human alveolar macrophages (AM) with heat-killed conidia from Aspergillus fumigatus and inert silica particles of similar size, about 3 microns, was studied. The conidia were phagocytized significantly faster by AM than were the control particles partly due to the faster rate of attachment but especially due to the faster rate of ingestion. Quantitative nitroblue tetrazolium (NBT) reduction by AM, reflecting their release of oxygen radicals, was increased by a factor of 2 to 3 in response to the conidia during phagocytosis. The silica particles induced a moderate but significant increase in NBT reduction. Conidia, but not silica particles, showed a considerable percentage (around 8%) of phagolysosomes with neutral pH after 3 h and a smaller percentage (around 1%) after 24 h of incubation. The pH of phagolysosomes with conidia tended to be higher after 3 h, but was significantly lower after 24 h than the pH of phagolysosomes with silica particles. Despite the markedly increased oxidative metabolism there was no increase in cytokine production [interleukins (IL) 6 and 8 and tumor necrosis factor alpha (TNF-alpha)] after exposure to conidia. The silica particles induced a significant decrease in IL-6 and IL-8 production and a tendency toward decreased production of TNF-alpha. The occurrence of phagolysosomes with neutral pH suggests unsealed phagolysosomes from which not only oxygen metabolites but also enzymes might escape from the cell. Lung damage may thus be the result of repeated or long-term exposure to Aspergillus conidia.