The uptake of 14C-ring labelled histamine and histidine was studied in human and guinea-pig leucocytes, and in rat peritoneal mast cells. Histamine uptake by sensitized human leucocytes was partly released by antigen or anti-IgE challenge, suggesting that histamine is taken up by the same cells that synthesize and secrete that amine, i.e. basophils. Histamine antagonists, particularly of the H2-subclass, had an inhibitory effect, but histamine agonists had a relatively small and inconsistent effect. Adrenoceptor stimulants and phosphodiesterase inhibitors produced small effects, but dibutyryl cAMP at a concentration of 4-10 mM consistently increased histamine uptake by more than 100% during a 30 min incubation. By contrast, ATP exerted an inhibitory effect, starting at a concentration of 0.2 mM and reaching a maximum (90% inhibition) at 10 mM. Histidine uptake was inhibited by ATP and slightly stimulated by cAMP. Propranolol caused stimulation of histamine uptake and inhibition of histidine uptake at micromolar concentrations. These results suggest that the uptake of histamine is not due to simple diffusion. Although it does not contribute significantly to total cell histamine content or to the removal mechanism of extracellular histamine, it may contribute to the auto-regulatory processes modulating histamine release, synthesis and metabolism. It may also have a significant effect on the extracellular level of histamine, under the influence of drugs or in pathological states.