Both the Ca(2+)-releasing mechanism induced by cyclic ADP-ribose (cADPR) and the ADP-ribosyl cyclase (ADPRC) activity that converts NAD(+) to cADPR were observed in a variety of cell types. We studied the ADPRC activity in rat major salivary glands that include parotid gland (PG), submandiblar gland (SMG), and sublingual gland (SLG). The enzyme activity responsible for cADPR synthesis was detected by spectrofluorometric assay using NGD(+) as a substrate. The enzyme activities in SLG, SMG, and PG were about 400, 30, and 40 nmol/min/g tissue, respectively, in 5-week-old rats. The highest value was observed in SLG and this value was higher than those in other tissues; e.g., spleen (200 nmol/min/g tissue). The enzyme activity in SLG increased gradually after birth and showed a maximum value at 3 weeks. On the other hand, the enzyme activities almost did not change in both PG and SMG between 0 and 9 weeks. In spite of the high ADPRC activity in SLG, we could not detect the cADPR-induced Ca(2+)-release from SLG microsomes. These results suggest that the ADPRC in SLG does not function through Ca(2+)-release observed in various tissues.