In the present study we compared the capabilities of sepharose-bound protein A versus protein G columns to remove in vitro lymphocytotoxic anti-HLA antibodies from sera of four highly sensitized renal transplant recipients (PRA greater-than-or-equal-to 70%). In none of the patients were protein A sepharose columns capable of completely removing anti-HLA antibodies, as demonstrated by the presence of residual alloreactive lymphocytotoxic activity in IgG 3 antibodies containing fractions eluted at pH 7. In contrast, no residual anti-HLA lymphocytotoxic antibody activity was found in fractions eluted at pH 7 from protein G columns. These data demonstrate that: (1) IgG 3 antibodies can be partly responsible for lymphocytotoxic anti-HLA reactivity in some sensitized renal transplant recipients and (2) at least in this patient category, in vitro immunoadsorption with protein G is more efficient than protein A sepharose columns in completely removing anti-HLA IgG antibodies from sera.