Human gastric mucosal cells were isolated by digestion of fundic biopsies with pronase and collagenase. The mean value of gastric cells per milligram biopsy specimen ± SEM was 59,000 ± 4,300 (n = 31) with a viability of 90 ± 5 %. With the cell yield of 1 patient a series of approximately 70 – 80 cyclic AMP measurements was possible. Histamine stimulated intracellular cyclic AMP production with an EC50 value of 35 ± 25 μmol/l (SEM; n = 4). In the presence of 100 μmol/l histamine the Ki values (μmol/l) for the histamine H2 receptor antagonists averaged 1.45 (cimetidine), 0.10 (ranitidine), and 0.02 (famotidine). No significant inhibition of histamine-induced cyclic AMP production was obtained with the histamine H₁ receptor antagonist triprolidine. With the new method histamine-induced cyclic AMP production can be measured in intact human gastric mucosal cells from fundic biopsy samples.