The aggregation of rat alveolar macrophages in the presence of platelet activating factor (PAF) is described. Male Sprague-Dawley- rats were used in these studies. Addition of PAF to a suspension of rat alveolar macrophages resulted in a rapid change in light transmitted through this cell suspension. The extent of PAF induced aggregation, calculated as a change in transmitted light per 1,000,000 cells per milliliter was 22.9 at a PAF concentration of 94.5 micromolar. Aggregation increased in a linear fashion with increasing cell number up to approximately 3,000,000 cells/milliliter. At cell concentrations greater than this, the extent of aggregation declined. Saturation of the aggregation effect was observed after 80 micromolar PAF concentrations were reached. The authors suggest that the PAF concentration required for half maximal response was similar for rat lung alveolar macrophages and type-II cells, whereas the extent of response of macrophages to PAF was only 66% of that elicited by type-II cells. The stereoisomer, enantio-PAF, and the C2-acetyl hydrolyzed product, lyso-PAF, each caused aggregation of isolated rat alveolar macrophages in a manner similar to that for PAF. The authors suggest that the response of rat macrophages described represents a toxic response to high levels of PAF.