We have investigated whether increased plasma protein leakage is present early after segmental allergen challenge in allergic asthma. Seven asthmatic subjects with mild allergy (AA group) and 5 non-asthmatic subjects with allergy (ANA group) were challenged with allergen doses based on similar early skin reactions; 5 healthy control subjects without allergy (C group) were challenged with the highest dose applied in the subjects with allergy, Bronchoalveolar ravage (BAL) fluid was obtained before, at 5 minutes after, and at 4 hours after challenge from different segments. Levels of albumin (Alb) and alpha(2)-macroglobulin (A2M) were measured in BAL fluid and serum. In addition, we calculated the relative coefficient of excretion as follows: RCE = ((A2M in BAL fluid)/(A2M in serum))/((Alb in BAL fluid)/(Alb in serum)). Also, levels of tryptase as a marker of mast cell activation and tumor necrosis factor-alpha (TNF-alpha), a possible inducer of plasma protein leakage, were determined. At 5 minutes after challenge, in none of the groups was a significant change found in the parameters for protein leakage. Levels of tryptase were increased in the subjects with allergy at 5 minutes after challenge only (P = .004), At 4 hours after challenge, levels of Alb (P = .03) and A2M (P = .04) and the RCE (P = .04) were increased in the AA group only. At 4 hours, levels of TNF-alpha were increased, with no significant differences among the three groups. In the asthmatic subjects with allergy, levels of TNF-alpha correlated with levels of Alb (r = 0.85, P = .02). In conclusion, at 4 hours after segmental allergen challenge, plasma protein leakage was increased in the asthmatic subjects only. The increase in levels of TNF-alpha in all groups indicates that the presence of TNF-alpha alone was not sufficient to cause plasma protein leakage within 4 hours after allergen challenge. Our results confirm the concept that plasma exudation after allergen exposure is a pathophysiologic event associated with asthma.