Southern bayberry, distributed throughout the southeastern United States, is the source of the fifth most common windborne tree pollen in Tampa, Fla. Fifteen percent of 400 consecutive subjects evaluated for allergic respiratory symptoms in the Tampa Bay area had positive skin tests to bayberry pollen extract. Bayberry pollen extract was obtained commercially and used to perform 25 nasal and 22 bronchial challenges on 45 subjects. Twelve of 13 (92%) study subjects with allergic rhinitis and positive skin tests to bayberry pollen extract and two of 12 (17%) control subjects with negative skin tests had positive nasal challenges (p = 0.0001). Four of seven (57%) study subjects with extrinsic asthma and positive skin tests to bayberry pollen extract and none of the 15 (0%) control subjects with negative skin tests had positive bronchial challenges (p = 0.001). Sera from 30 subjects who underwent 31 challenges were assayed for bayberry pollen extract-specific IgE by plate radioimmunoassay. Specific IgE antibodies were present in the sera of 8 of 13 (62%) subjects with positive challenges and absent in 15 of 18 (83%) subjects with negative challenges (p = 0.01). Intradermal skin tests with bayberry pollen extract were more predictive of provocation challenge results than plate radioimmunoassay (positive predictive value of 80%, 95% CI 62% to 98%; versus 73%, 95% CI 47% to 99%). Bayberry pollen extract is allergenic, and the Southern bayberry tree fulfills Thommen's criteria defining aeroallergen-producing plants.