Interleukin-1 (IL-1) promotes cell recruitment and influences allergic mediator release. We analyzed histamine, prostaglandin D2, IL-1, and leukocytes accumulating hourly for 12 hours at skin-chamber sites after local ragweed challenge in eight allergic subjects with cutaneous late-phase reactions. Ragweed induced a peak of histamine at 1 hour (p less than 0.02), which diminished, and then steadily increased (p less than 0.02). Prostaglandin D2 levels peaked by the second hour (p less than 0.02) and then decreased, approaching prechallenge levels by 12 hours. Leukocyte infiltration (predominantly neutrophils) was detectable 3 to 4 hours after challenge, although selective enrichment of mononuclear cells, eosinophils, and basophils ws observed at later hours (p less than 0.02). IL-1 bioactivity was detected in fluids 10 to 12 hours after challenge but not at control sites (p less than 0.05). Analysis of IL-1 beta levels by RIA revealed an initial peak at 1 hour of 0.90 ng/ml (p less than 0.02) and a second elevation of up to 0.75 ng/ml during the later hours (p less than 0.04). Ragweed challenge of three nonatopic subjects did not change levels of the above-mentioned mediators or cells. Bioactivity in chamber fluids from antigen-challenged sites of atopic subjects was significantly neutralized by an anti-IL-1 beta antiserum, although treatment with anti-IL-1 alpha and anti-IL-1 beta was needed for complete neutralization, IL-1 released locally during cutaneous allergic reactions may contribute to IgE-dependent cutaneous inflammation.