Changes of alkaline phosphatase in small intestine, liver, kidney, bone and serum of rats administered 100 ppm (890 nM) of Cd2+ in the drinking water were observed during a 12 months period. After 2 weeks of cadmium administration, decreases in bone and small intestine alkaline phosphatases in serum of Cd-exposed rats were observed by a polyacrylamide gradient gel electrophoresis and the alterations continued through the 9th month of administration. At one month, the activities of the alkaline phosphatase fractions, p-1 and p-2, obtained from Sephadex G-200 column gel filtration of bone extracts from Cd-exposed rats were 32% and 43% of those in the controls, respectively, whereas Cd accumulation in the bone was very low (9 nmol/g wet weight). After 3 months, osteoporotic changes of bone and erosion of submucosa layer of the small intestine were observed by light microscopy. Alkaline phosphatase in small intestine of the Cd-exposed rats was 60% of that in the controls after 3 months. At 12 months, the decreased activity of bone alkaline phosphatase in Cd-exposed rats recovered to the same level as activity in the non-exposed rats. Moreover, the activity in kidney of the Cd-exposed rats was 80% of that in the controls. However, histological conversion from osteoporotic to osteomalacic changes in bone and kidney lesions by Cd administration were not observed by light microscopy. Liver alkaline phosphatase activity of the Cd-exposed rats did not change even at 12 months, whereas 1.2 mumol of Cd per g wet weight accumulated in this organ.