We found the high molecular mass intestinal alkaline phosphatase (HIAP) and normal molecular mass intestinal alkaline phosphatase (NIAP) in serum at fasting and after fatty meal by use of 6.0% olyacrylamide gel electrophoresis (PAGE) in the presence of 1% Triton X-100. HIAP only ppeared in serum of Lewis blood group secretors {Le(a − b +)}, and HIAP levels were dependent on ABO blood groups. Among the secretors, the highest activities of HIAP in fasting serum were observed in subjects with blood groups O and B (8.6 ± 1.4 U/1; mean ± SD) and the lowest activities were associated with blood group A (0.7 ± 0.2 U/1; mean ± SD), and the HIAP activities did not change after fatty meal. In contrast, NIAP was present in the serum of both secretors and non-secretors regardless of ABO blood group. Trace amounts of NIAP remained in fasting serum; however serum NIAP activities rose sharply after fatty meal. The remaining ratios of NIAP activity at fasting and 9 h after fatty meal of secretors were approximately the same as those of nonsecretors. The electrophoretic mobility on PAGE or the apparent molecular mass estimated by gel filtration of serum NIAP in secretors was slightly different from that in non-secretors. In addition, HIAP can be normalized to NIAP on PAGE in the absence of Triton X-100, and the electrophoretic mobility of normalized-NIAP was identical to that of original NIAP in secretors. Accordingly, it can be concluded that the structure of serum NIAP in the secretor was different from that in the non-secretor, because HIAP is only formed by serum NIAP in the secretor. These results suggest that differences in serum NIAP in the secretor and the non-secretor may be closely related to the appearance of IAP in the circulation.