Monocytes are inflammatory cells that accumulate in the airway in asthma. Monocytes constitute a heterogenous cell population in normal subjects. The heterogeneity of monocytes from nine patients with mild asthma and nine normal subjects was studied by means of discontinuous density gradient centrifugation with use of bovine serum albumin. The rate of low-density monocytes recovered from patients with asthma was higher than that obtained from normal subjects. The functional activity of monocyte fractions from asthmatic and control subjects was assessed by using the release of interleukin-1β (IL-1β) and the intensity of lysosomal enzymes, such as acid phosphatase and nonspecific esterase. The low-density cells produced less IL-1β than did cells of higher density in normal subjects. The IL-1β release was increased in low-density monocytes from subjects with asthma when compared with the same fraction from normal subjects (p < 0.01). The low-density monocytes had a higher activity of lysosomal enzymes than did cells of higher density in both asthmatic and normal subjects. Electron microscopic studies showed that low-density monocytes from the subjects with mild asthma appeared to have the morphologic characteristics of activated cells with more vacuoles in this periphery. This study shows that low-density monocytes from subjects with asthma retain the ability to be activated in vivo and in vitro and may orchestrate immune reactions in mild asthma. (J ALLERGY CLIN IMMUNOL 1995;96:230-8.)