Binding of D-Penicillamine (D-Pen) to human monocytes was examined by flow cytometry with fluorescent D-Pen conjugate. Cells from HLA DR1-positive healthy females bound significantly more D-Pen than cells from DR1-negative healthy females (P=0.015), and DR1 was associated with the highest binding among HLA DR antigens. In contrast, DR4 was associated with the lowest binding in healthy females. A difference in D-Pen binding between healthy females who were DR1-positive, DR4-negative and those who were DR1-negative, DR4-positive was statistically significant (P=0.026). Neither healthy females nor healthy males showed significant associations of D-Pen binding with HLA A, B, or C antigens, nor did healthy males show an association between strength of D-Pen binding and any DR antigens.