Histamine release has been detected biologically after exposure of human right atrial biopsy samples to compound 48/80. Human right atrial samples contain large quantities of histamine, 1035 +/- 65 ng/g fresh weight. Exposure of untreated electrically paced atrial strips to compound 84/80, 300 micro/ml, caused an increase in the force of atrial contraction similar to that caused by histamine. Pretreatment of strips with cimetidine, 3.16 x 10(-5) M, prevented the inotropic response to compound 48/80. It is concluded that mast cell degranulation in human atrial tissue can cause sufficient release of histamine to modify the function of the heart.