1. Noradrenaline and histamine, when added to superfused guinea-pig cerebral-cortical tissues, increased both cyclic AMP-dependent and -independent histone kinase activities of some, but not of all, subsequently isolated subcellular fractions, and decreased their cyclic [3H]AMP-binding capacity, which was concluded to be due to an increase in endogenously bound cyclic AMP. 2. Adenosine and 2-chloroadenosine also diminished the cyclic [3H]AMP-binding capacities, but did not affect the histone kinase activities. 3. DEAE-cellulose chromatography and stability to KCl additions showed that the greater part of the histone kinase of the present preparations corresponded to the type II enzyme [of Corbin, Keely & Park (1975) J. Biol. Chem.250, 218–225], with a lesser amount of type I activity. Different sites of cyclic AMP accumulation in relation to these or other kinases are considered in interpreting the differential tissue responses to the neurohumoural agents examined.