DNA synthesis, as monitored by ('3)H-thymidine incorporation, in the germinative stem cells of juvenile Hymenolepis diminuta, appears to be negatively modulated by increases in cyclic-3'5'-adenosine monophosphate (cAMP). Among the endogenous substances which elevate cAMP levels in these worms is serotonin, a.k.a. 5-hydroxytryptamine (5HT). High concentrations of exogenous 5HT, or treating worms with reserpine which presumably induces a secretion of endogenous 5HT, similarly depresses DNA synthesis. These findings suggest that factors such as 5HT, which increase worm cAMP levels, may negatively modulate stem cell proliferation in these tapeworms. This event could trigger the onset of stem cell differentiation, following the principle that, in general, cells 'switch off' their divisional activity in order to 'switch on' biosynthesis directed to more specialized structure and function. As recognized many years ago by Grobstein (1963), in a given cell, specialized synthesis (for differentiation) and preparation for continued division (DNA replication) are usually competitive and may, in many instances, be exclusive events. In fact, dibutyryl cyclic adenosine monophosphate (DBcAMP), 5HT and isobutylmethylxanthine (IBMX) which are factors that elevate cAMP in these worms, and depress their DNA synthesis, tend to enhance ('3)H-uridine incorporation ergo RNA synthesis. A large number of the stem cell population are, then, slowing their divisional activity to either differentiate or withdraw into the G(,1) or, less probably, into the G(,2) phase