Subclasses of lung immunoregulatory T cells were analyzed during acute pulmonary inflammation in strain 2 guinea pigs and compared with T cell subpopulations in the peripheral circulation. Immunized animals were aerosol-challenged with specific antigen and sacrificed at 12-, 24-, 48-, 72-, and 96-hours postchallenge. Mononuclear cells, isolated from peripheral blood and bronchoalveolar lavage, were enriched for T cells. The percentage of helper T cells, as well as antigen-specific blastogenesis, in recovered pulmonary T cells exhibited maximal values at 12-, 24-, and 96-hours postchallenge. In contrast, the presence of suppressor T cells correlated with decreased blastogenesis and antigen-specific suppression in isolated lung cells at 72-hours postchallenge. Since changes in pulmonary cells did not correlate with those found in the peripheral circulation, immunoregulatory events in these two compartments may be distinct. These results indicate that the proportions of lung T cell subclasses, as well as their in vitro functional activity, are altered over the course of pulmonary disease. Such changes in immunoregulatory cell populations may be important in the mediation of disease pathogenesis.