Phagocytosis was investigated using human peripheral monocytes and erythrocytes sensitized with known amounts of subclass-specific IgG anti-Rh antibodies. The erythrocyte-bound IgG was quantitated by a radiometric antiglobulin test. This evaluation revealed the following: (1) there is a relationship between phagocytosis and the number of erythrocyte-bound IgG molecules; (2) phagocytosis is IgG subclass-dependent, since a similar degree of phagocytosis is observed with fewer IgG3 than IgG1 molecules and also the minimum number of IgG3 molecules for phagocytosis is 150-640, whilst for IgG1 the minimum is 1,230-4,020; (3) the minimum levels of sensitization for phagocytosis should be detectable by the serological antiglobulin test; (4) the phagocytosis assay is no more sensitive than the monocyte rosette assay for the detection of anti-Rh alloantibodies, and (5) phagocytosis of adherent erythrocytes observed by video-enhanced microscopy indicated that erythrocytes may adhere to monocytes for a considerable time before phagocytosis, but that phagocytosis itself was rapid.