Serum immunoreactive cationic trypsinogen (ICT) response to bolus injection of secretin (1 Clinical Units/kg of body weight) has been evaluated in 123 normal controls and related to sex, age, smoking habit, and alcohol and coffee consumption. A 100% increase of serum immunoreactive cationic trypsinogen levels after secretin has been considered as a positive response (R+). When the population was considered as a whole, 55% of subjects proved to be R+ and the remaining were R-. In the R+ group the serum immunoreactive cationic trypsinogen response was appreciated as early as 5 min after secretin and even after 2 min in the few cases in which it was evaluated. It is suggested that this direct leakage of the proenzyme from the pancreas may be due to an increased sensitivity of the pancreas to secretin. Coffee consumption and age of subjects did not affect the test. Male sex, smoking habit, and alcohol intake were associated with a significantly higher percentage of R+. Therefore, we suggest that alcohol and smoking might result in the development of biochemical abnormalities in pancreatic function before the appearance of clinical evidence of pancreatic disease.