We investigated the role of beta2 (CD18) and alpha4 (CD49d) integrins in eosinophil and neutrophil recruitment to lung parenchyma and bronchoalveolar lavage fluid (BALF) of allergen-challenged Brown Norway (BN) rats. Challenge of sensitized BN rats with ovalbumin induced an eosinophil- and neutrophil-rich infiltrate in BALF at 24 h, accompanied by an increase in BALF protein content. Treatment with either the TA-2 monoclonal antibody (mAb) against alpha4 (as an F[ab']2 fragment) or the WT.3 mAb against beta2 integrin significantly reduced eosinophil and neutrophil accumulation in BALF by 54 to 66% and eosinophil accumulation in the parenchyma by 48%. A significant difference in effect was observed between mAb TA-2 in intact immunoglobulin G or F(ab)2 form. Combined treatment with mAbs WT.3 plus TA-2 (F[ab]2) virtually abolished eosinophil accumulation in BALF and in the parenchyma, and reduced neutrophil accumulation in BALF by 91%. In contrast, neutrophil accumulation in the lung was not inhibited by these mAb treatments. The increase in BALF protein concentration was significantly inhibited by TA-2 (by 40%) and by WT.3 plus TA-2 in combination (71% inhibition). We conclude that eosinophil and neutrophil migration into the air space in allergic lung inflammation is partially CD18 (beta2)- and CD49d (alpha4)- dependent and that alpha4 integrins mediate essentially all of the CD18-independent migration. Similarly, eosinophil accumulation in the parenchyma is completely alpha4 and CD18 (beta2) integrin-dependent. In marked contrast, neutrophil accumulation in the lung in this allergen model can occur independently of both alpha4 and beta2 integrins.