Three different ben,odia,epines (diazepam, its pharmacologically active metabolite desmethyldiazepam, and the derivative chlordesmethyldiazepam) have been compared in our study for their effects on 3',5'-guanosine monophosphate (cGMP) cerebellar levels. Desmethyldiazepam and chlordesmethyldiazepam are several-fold more potent than diazepam in decreasing rat cyclic cGMP cerebellar concentrations. None of the three drugs induces detectable changes of cerebellar cyclic 3',5'-adenosine monophosphate (cAMP). On the other hand, the three compounds did not modify the levels of cGMP in cerebellum of newborn rats, where Purkinje cell and dendrites lack synaptic contacts. However, injection of gamma aminobutyric acid (GABA) in the newborn is still able, as in the adult, to decrease cGMP concentration in cerebellum. Our data support the hypothesis that cGMP cerebellar concentrations may be reliable biochemical marker of the clinical activity of benzodiazepines.