High amounts of fungal spores, bacteria, and bacterial endotoxin have been found in dust associated with the poorly characterized syndrome, organic dust toxic syndrome (ODTS). As part of an ongoing investigation to determine the etiopathogenesis for ODTS, this study has focused on activation of guinea pig bronchial alveolar lavage (BAL) cells as evidenced by the production of superoxide anion in response to fungal spores and lipopolysaccharide (LPS). Fungal spores from Aspergillus candidus, Aspergillus terreus, Aspergillus niger, Aspergillus fumigatus, Eurotima amstelodami, Penicillium spinulosum, and Cladosporium cladosporioides were all shown to increase superoxide anion production, each with different potencies. LPS stimulated little superoxide anion production in BAL cells, but when cells were pretreated with LPS prior to stimulation with fungal spores, superoxide anion production was increased over that induced by either spores or LPS alone. These results suggest that the inhalation of LPS together with fungal spores could possibly provoke abnormal lung pathologies.