E-rosette-forming cells (E-RFC) in human peripheral blood can be subdivided into two fractions on the basis of their relative affinity for sheep red blood cells (SRBC). “High-affinity” E-RFC constituting 54 ± 5% of normal mononuclear cell suspensions are capable of rosette formation, despite elevated temperatures of incubation (29°C) with limited numbers of SRBC. “Low-affinity” E-RFC constituting 23 ± 4% of peripheral blood mononuclear cells require cool temperatures of incubation with an excess of SRBC to form rosettes. The following evidence indicates that low-affinity E-RFC bear surface receptors for the Fc portion of IgG, whereas high-affinity E-RFC do not. a) When High-affinity E-RFC were isolated from mononuclear cell suspensions, very few (2 ± 1%) of these lymphocytes formed rosettes with IgG-sensitized chick red blood cells (EA). When the remaining low-affinity E-RFC were then isolated, up to 85% formed rosettes with chick EA. b) When lymphocytes were incubated with erythrocyte monolayers sensitized with high concentrations of IgG, low-affinity E-RFC adhered to these EA monolayers. High-affinity E-RFC failed to attach to immune complexes. c) Virtually all E-RFC in thymus, tonsil, and lymph node formed high-affinity E rosettes and failed to bind chick EA. Spleen cell suspensions, on the other hand, contained a low-affinity E-RFC subset and E-RFC capable of binding chick EA. d) The proportion of low-affinity E-RFC in the peripheral blood of normal subjects correlated closely with the proportion of Fc-positive E-RFC among the mononuclear cells of those individuals. These observations suggest a close association between the presence of the Fc receptor on human T cells and the affinity with which those cells bind SRBC. Modified E rosette procedures permit rapid identification or isolation of high-affinity, Fc-negative and low-affinity, Fc-positive E-RFC subpopulations.