There is considerable evidence to support the idea that the cyclic nucleotide system plays an important role in the pathophysiology of bronchial asthma, allergic and vascular diseases. Ancient Chinese medical prescriptions which were used to treat these diseases have been described, and accordingly, tests were performed on those same herbs to assay for the possible presence of cyclic nucleotides, both cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP). Water extracts of 180 different herbs were tested for cyclic AMP and cyclic GMP activity by a competitive binding assay and a radioimmunoassay. Of these only the fruit of
Zizyphus
jujuba
(
Z
.
jujuba
) was positive for cyclic AMP activity, and its fruit and fruit of
Evodia rutaecarpa
(
E
.
rutaecarpa
) were positive for cyclic GMP activity. The cyclic AMP and cyclic GMP active substances were eluted by methods known to isolate cyclic nucleotide using Bio-Rad AG 1x4 and alumina columns. The purified samples of cyclic AMP and of cyclic GMP showed the same physicochemical properties as authentic cyclic AMP and cyclic GMP respectively, using different solvents, by UV spectroscopy, and by high pressure liquid chromatography (HPLC). After incubation with cyclic nucleotide-specific phosphodiesterase at 37°C for 60 min., most of the cyclic AMP or cyclic GMP isolated from those plants disappeared and 5′-AMP or 5′-GMP was detected by thin-layer chromatography (TLC). These results indicate that the isolated substances from these herbs are cyclic AMP and cyclic GMP. The fruit of
Z
.
jujuba
contains about 500 nmole/g cyclic AMP and 50 nmole/g cyclic GMP respectively and the fruit of
E
.
rutaecarpa
contains about 40 nmole/g cyclic GMP. These values of cyclic nucleotides were higher than previously reported in either plant or animal tissue. Only small amounts of cyclic AMP were detected in immature fruit of
Z
.
jujuba
indicating that cyclic AMP in this fruit increases and accumulates during the maturation. Existence of cyclic GMP was also demonstrated in the other species of Evodiae genus, and comparable amounts were detected in fresh unripened fruit of
E
. rutaecarpa. There have been several reports on the existence of small amounts of cyclic AMP among the higher plants. On the other hand, only a few reports have shown the existence of cyclic GMP among higher plants. The pharmacological action of these oriental herbs may be due to the existence of these cyclic nucleotides.