The aim of our study was to determine whether first-phase insulin response to intravenous (i.v.) glucose could be used as a simple and rapid test to identify cystic fibrosis (CF) patients at risk to develop diabetes mellitus. Forty consecutive CF patients with normal fasting blood glucose values but with different degrees of glucose tolerance on the standard oral glucose tolerance test (22 with normal glucose tolerance, 16 with impaired glucose tolerance, 2 with diabetes mellitus) and 12 normal subjects, matched for age and body mass index, underwent an i.v. glucose bolus to evaluate early phase insulin release. When compared to the normal subjects, CF patients had significantly reduced basal (76 +/- 50 vs 108 +/- 30 pM/l, 2 p < 0.02) and glucose stimulated insulin levels (1 + 3 min insulin = 456 +/- 275 vs 951 +/- 170 pM/l, 2 p < 0.01). Early phase insulin release, however, did not differentiate between CF patients with normal and impaired glucose tolerance; also in the two diabetic patients insulin levels did not clearly differ from those observed in the other groups of CF subjects. In conclusion, first-phase insulin response may identify an impairment of B-cell function in CF subjects; however, it does not discriminate between different degrees of glucose tolerance, as determined by the oral glucose tolerance test and, therefore, it does not reliably identify those patients who will eventually develop overt diabetes mellitus.