The platelet antigen N(aka) was once considered to be a platelet-specific alloantigen and is carried on platelet membrane glycoprotein (GP) IV. Recent studies suggest that N(aka)-negative subjects lack platelet GPIV. GPIV is an important adhesive receptor and expressed on the surface of monocytes as well as of platelets. In the present study, flow cytometry was used to detect GPIV and N(aka) antigen on the surface of monocytes. N(aka) antigen was expressed on monocytes as well as on platelets in N(aka)-positive subjects (n = 6) (P-GPIV-positive subjects). To our surprise, monocytes of N(aka)-negative subjects (n = 7) (P-GPIV-negative subjects) having no anti-N(aka) antibody in their serum expressed GPIV and N(aka) antigen to almost the same degree as did the monocytes of P-GPIV-positive subjects. Competitive experiments using OKM5 (a monoclonal antibody against GPIV) and anti-N(aka) antibody showed that the epitope of anti-N(aka) antibody on monocytes was very close to that of OKM5. In two P-GPIV-negative subjects having anti-N(aka) antibody in their serum, GPIV and N(aka) antigen were not expressed on the surface of either monocytes or platelets. These results indicate that the GPIV molecules and N(aka) antigen are expressed on the surface of monocytes in the majority of P-GPIV-negative subjects, but that in a very few P-GPIV-negative subjects neither GPIV nor N(aka) antigen is expressed on the surface of their monocytes. We hypothesize that P-GPIV-negative subjects who carry neither GPIV nor N(aka) antigen on their monocytes produce anti-N(aka) antibody as a result of transfusion or pregnancy.