Compared to the obvious phenotypic and functional heterogeneity of tissue macrophages, little information is available on subsets of blood monocytes. We have employed two-color immunofluorescence and flow cytometry for the definition of regular and small monocytes, the latter characterized by the low-density expression of CD 14 and the strong expression of the CD 16 (Fcy-RIII) antigen. These cells comprise 15% of the blood monocytes and they appear to be similar in phenotype to the alveolar macrophage. The CD14+/CD16+ small monocytes can perform phagocytosis and they produce reactive oxygen, while their capacity for cytokine production is strongly reduced when compared to regular monocytes. At this point it is still unclear as to whether the CD14+/CD16+ small monocytes comprise a specific level of activation or differentiation or a distinct sublineage of human blood monocytes.