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Dictyostelium discoideum is a slime mold that exists in a unicellular amoeboid form under certain nutritional conditions. In this form, it produces unique lysosomal enzymes that are valuable in studying cell-to-cell signaling systems. We report on a research microbiologist who developed rhinoconjunctivitis and asthma after release of D. discoideum from a pressurized canister. Immediate skin test reactivity was demonstrated to whole and lysed organisms. Enzyme-linked immunosorbent assay results revealed IgE antibody against D. discoideum whole organism, lysed organism, and lysosomal enzymes with the strongest response being directed toward lysosomal enzymes. Pulmonary function testing showed a decline in forced expiratory volume in 1 second and forced expiratory flow after modified laboratory exposure to D. discoideum. This case represents the first report of occupational rhinoconjunctivitis and asthma from slime mild.