The isotype specificity of Fc-receptors for IgG (Fc gamma-Rs) on normal guinea pig splenic B and T cells was determined by a rosette assay using sheep erythrocytes sensitized with either homologous IgG1 or IgG2 anti-sheep erythrocyte antibody [EA(IgG1) or EA(IgG2)]. Approximately 70% of the lymphocytes in the highly purified B-cell fraction could form rosettes with EA(IgG2), and 55% of the cells with EA(IgG1). Inhibition experiments with soluble complexes of IgG1 or IgG2 antibody with ovalbumin demonstrated that approximately 20% of the EA(IgG2) rosette-forming B cells bore the Fc gamma-R monospecific for IgG2, whereas 80% of the cells had two distinct Fc gamma-Rs simultaneously; one monospecific for IgG2 and the other bispecific for IgG1 and IgG2. The existence of a B cell bearing the Fc gamma-R monospecific for IgG1 was not definitively demonstrated in the B-cell fraction. In the T cell-enriched fraction, approximately 40% of the cells could form rosettes with EA(IgG2). The EA(IgG1) rosette-forming cells, however, comprised only 6% of the total cells, indicating that most of the EA (IgG2) rosette-forming T cells bear essentially the Fc gamma-R monospecific for IgG2 alone. The results obtained revealed that guinea pig splenic lymphocytes bear two distinct Fc gamma-Rs, which are not equally distributed on the B- and T-cell populations and also on their respective subsets.