Basophil leukocytes from human blood secrete histamine in the absence of a membrane stimulus when incubated in a medium containing Sr2+, 1-10 mM. Spontaneous histamine secretion in the presence of Sr2+ is inhibited by La3+, 1-1000 nM and 2 deoxy-D-glucose, 30-300 .mu.M. Spontaneous secretion in the presence of Sr2+ increases with increasing pH in the range 6.5-8.5. Agents which cause a rise of intracellular cyclic[c]AMP level increase the spontaneous secretion in the presence of Sr2+. The results suggest that spontaneous histamine release is a secretory response of the cells and evidence is provided for a dual role of cAMP in the control of histamine secretion.