The inhibitory effect of HLA antisera on Fc receptors of human lymphoid FcRFC and K cells was investigated. Antisera recognizing determinants of the HLA-A, -B, and -C series had no effect on FcRFC, while specific inhibition was observed with an antiserum reacting with determinants closely associated to HLA-DW2. This inhibitory effect was also demonstrated by the Fab' fragments. Specific inhibition of K cells was observed with all HLA antisera, but this effect was lost in the Fab' fragments. We concluded that the Fc receptor of FcRFC may be closely associated with products of the HLA-D region. This is analogous to the association between the Fc receptor and the Ia antigens on murine splenic B lymphocytes.