Oetreotide (OCT) administration provides a biochemical cure in most acromegalic patients. This drug, however, causes several side effects and is very expensive. Acute testing has been reported to predict chronic responsiveness to OCT administration. The aim of this retrospective study was to evaluate which test, if any, among acute testing, short-term (1 month) administration, and In-111-pentetreotide (In-111-DTPA-Phe-D-OCT) scintigraphy, is best in predicting response to long-term OCT treatment. Sixty-eight patients with active acromegaly were studied. An acute test (100 mu g sc OCT) was performed as usual: a GH decrease greater than or equal to 50% of baseline was considered a positive response. GH and insulin-like growth factor I(IGF-I) were then assayed after 1 month (300 mu g daily) and 3 months (150-600 mu g daily) of OCT administration. GH was considered normalized when decreased less than or equal to 5 mu g/L. Twenty-six of 68 patients were subjected to In-111-pentetreotide scintigraphy. Linear correlation analysis of the results was performed. Sensitivity, specificity, and positive and negative predictive values of the three tests were also calculated. Thirty-eight of 68 patients (56%) responded to the acute test. Among these 38 patients, 20 experienced normalization of GH and IGF-I levels during long-term therapy, as did 8 patients who did not respond to the acute test. No significant correlation was found between GR percent decrease during acute testing and long-term therapy (r = 0.11). Seven patients who responded to the acute test and 2 who did not respond had adenoma shrinkage during therapy. Conversely, GH and IGF-I decrease after short-term treatment significantly correlated with long-term treatment (r = 0.76 and 0.64, P < 0.01). Of the 26 patients subjected to In-111-pentetreotide scintigraphy, 13 had significant tracer uptake: normalization of GH and IGF-I was obtained in 8 patients. A significant col relation was found between tracer uptake and GH/GF-I inhibition after 3 months of therapy (r = 0.6; P < 0.05), In the whole population, the positive predictive value of acute testing, short-term OCT administration, and In-111-pentetreotide scintigraphy was 53%, 70%, and 73%, respectively, when the GH nor normalization (< 5 mu g/L) after 3 months of therapy was considered, Moreover, In-111-pentetreotide scintigraphy had the highest specificity (100% in patients with baseline GH values below 50 mu g/L) compared with that of acute testing and short-term OCT administration. The acute test cannot be considered as a valuable index to identify patients' responsiveness to long-term OCT therapy, but it can be useful to test tolerability. By contrast, 1 month of OCT administration or the in vivo imaging of somatostatin receptors by In-111-pentetreotide might better indicate the patients who might effectively benefit from this treatment.