In the first step of the present study we re-examined the question whether HLA class I molecules isolated from human lymphocytes can bind to intact bacteria. HLA antigens were isolated from the lymphoblastoid cell line HOM-2 and incubated with the bacteria Yersina enterocolitica. Significant binding of antigens to the bacteria was detected whether the antigens were solubilized in the detergent NP 40, reconstituted in liposomes or presented as papain cleaved molecules. Next, we studied the specificity of the binding. We compared the ability of NP 40 solubilized HLA antigens derived from four different cell lines, expressing different HLA-A, -B and -C antigens, to bind to nine different strains of bacteria. Remarkably, few differences were found in that each strain of bacteria bound 10-30% of the HLA antigens derived from any of the four cells lines. Further, after a sample of HLA antigens had been incubated with one strain of bacteria, the unbound HLA antigens would fail to bind to another strain. The conclusions are as follows. First, we have confirmed a previous report that HLA class I antigens could bind to bacteria. Second, binding to bacteria is mediated through the extracellular portion of the HLA molecules which is not affected by papain cleavage. Third, it is the non-polymorphic areas of the HLA antigens which are responsible, because antigens purified from cell lines with different HLA-A, -B and -C allotypes have similar binding ability. Lastly, the binding of bacteria to HLA antigens is a universal phenomenon which does not distinguish one strain of bacteria from another.