Population and family studies of five sera with antibodies against B-cell determinants show an excellent fit of some of them with the HLA-D determinants, suggesting that the HLA-D determinants themselves or closely linked structures can be recognized by serology. One serum, Ag, might be coded for by a locus different from HLA-D, which could be located between HLA-A and -B. A two-color fluorescence test to detect B-cell antigens was used and found to save time and reagents and to give very good results.