Platelet membrane glycoprotein (GP) IV (also called CD36 and GPIIb) deficiency is associated with N(aka)-negative platelets. Using flow-cytometric analysis of cells stained with the monoclonal anti-GPIV antibody OKM5, we have studied the expression of GPIV on the monocytes from 16 healthy Japanese individuals whose platelets were deficient in GPIV. GPIV was absent on the surface of monocytes from 2 platelet GPIV-negative donors (type I), whereas it was present on the monocytes from the remaining 14 platelet GPIV-negative donors (type II). The fluorescent intensity of OKM5-stained type II monocytes was significantly (P < .05) lower than that of normal monocytes derived from platelet GPIV-positive donors, suggesting that the expression of GPIV on the type II monocytes is also abnormally regulated as compared with that on normal monocytes. OKM5 induced an oxidative burst in the type II monocytes as well as in the normal monocytes, but it failed to induce it in the type I monocytes. Because the 2 individuals with the type I deficiency have been healthy and exhibited no immunologic problems, GPIV appears to be not essential for the normal physiologic functions of monocytes. An anti-GPIV antibody was detected in the serum from one of the type I GPIV-deficient women, who had never received any blood transfusions but had given birth to three apparently healthy children. These results suggest that type I GPIV-deficient individuals may be at risk of developing an anti-GPIV isoantibody upon blood transfusion or pregnancy.