Alkaline phosphatase activity in obese mice (C57BL/6J ob/ob) was significantly increased from 18 to 63 weeks of age when compared to that of their lean controls (C57BL/6J +/?). In 5 week old animals, the earliest age examined, the circulating activity of alkaline phosphatase was similar in both obese mice and their lean counterparts. To characterize the circulating alkaline phosphatase activity in the obese mouse and its lean counterpart, the response of the enzyme to fasting, various inhibitors, heat inactivation, and urea denaturation was examined and compared. L-homoarginine and L-p-bromotetramisole inhibited to a large extent the circulating activity of alkaline phosphatase in both obese mice and their lean controls in the fed state, while L-phenylalanine had essentially no effect. Even though the response of alkaline phosphatase in plasma to several inhibitors was similar, the rate of denaturation by urea of enzyme activity in plasma was significantly slower in obese mice than in their lean controls in the fed state. While the rate of inactivation of alkaline phosphatase activity in plasma for the initial two minutes at 56 degrees C was similar in obese mice and their lean counterparts, the subsequent rate of heat inactivation was significantly slower in the plasma from obese mice. Thus, both obese and lean mice in the fed state have a circulating activity of alkaline phosphatase in plasma with a greater contribution from a skeletal isoenzyme and a lesser one of intestinal origin.(ABSTRACT TRUNCATED AT 250 WORDS)