The effects of Actinobacillus (Haemophilus) pleuropneumoniae and its metabolites on the oxygenation activity of porcine pulmonary alveolar macrophages (PAM) were studied, using a chemiluminescence technique. Actinobacillus pleuropneumoniae strains of serotypes 2, 3, and 9 in a dose of 1, 10, and 100 colony-forming units/macrophage first stimulated the oxygen radical production of PAM. After having reached a peak value, oxygenation activity decreased, finally resulting in total suppression of PAM. All these effects were neutralized by homologous convalescent pig sera that had been adsorbed onto inactivated A pleuropneumoniae strains. Moreover, cross-neutralization was shown between serotypes 2 and 3. Inactivated A pleuropneumoniae strains did not influence the oxidative activity of PAM. Undiluted and lower dilutions of sterile A pleuropneumoniae culture supernatants were toxic for PAM, whereas higher dilutions of the supernatants stimulated oxygen radical production of the macrophages. These effects were heat-sensitive and were neutralized by homologous convalescent pig sera. Cross-neutralization was shown between serotypes 2 and 3. These findings indicated that stimulation and inhibition of the oxygenation activity of PAM are attributable to heat-sensitive metabolites produced by A pleuropneumoniae.