The natural course of pain in chronic pancreatitis was followed up in 318 patients over 10.6 +/- 8.0 years (median, 9.0 years). By the end of our follow-up, a significant decline in pain in alcoholics (n = 228) and nonalcoholics (n = 90) (p < 0.001 and p < 0.03) was marred by the fact that, even after more than 10 years, 50% of alcoholics and 62% of nonalcoholics still reported pain attacks (difference insignificant). Only alcoholics had pain relief with increasing exocrine pancreatic insufficiency (p < 0.02), but 54% of alcoholics and 73% of nonalcoholics still had pain attacks despite severe, enzyme substitution-requiring exocrine pancreatic insufficiency. The development of severe endocrine pancreatic insufficiency did not significantly influence the course of pain. It is concluded that no clinically relevant differences exist in the course of pain in alcoholic and nonalcoholic chronic pancreatitis.