Hormonally active neuroendocrine tumors may easily be diagnosed by elevated serum levels of their specific peptides and hormonal products, but there are no reliable markers for neuroendocrine tumors without hormonal activity. Chromogranin A (CgA), a secretory protein of neuroendocrine cells, has recently been characterized as a valuable tissue marker in hormonally active and non-functioning neuroendocrine tumors. This study analyzes the role of CgA as a serum marker for different neuroendocrine tumors. Thirty-three patients with neuroendocrine tumors of the stomach (n = 7), the ileum (n = 18), and the pancreas (n = 8) were investigated. Serum CgA levels were analyzed by radioimmunoassay at the time of diagnosis and during follow-up under different therapeutic regimens. Serum CgA was elevated in 30 (91%) patients. Mean CgA serum levels varied with tumor location (pancreas: 7068 +/- 3008 ng/ml, ileum: 5381 +/- 1740 ng/ml, stomach: 529 +/- 179 ng/ml, x +/- SEM ng/ml) but did not differ between functioning and non-functioning tumors. Eight of 10 patients treated with either somatostatin or interferon-alpha showed changes of CgA concentrations corresponding to tumor growth. We conclude that CgA is a useful broad-spectrum tumor marker in gastroenteropancreatic neuroendocrine tumors. Its determination is especially recommended in tumors without hormonal activity.