The influence of total parenteral nutrition (TPN) was studied in 67 patients with severe acute pancreatitis having three or more criteria according to Ranson (mean +/- SD = 3.8 +/- 0.21). Although TPN has been reported to not be of benefit in the progress and severity of the disease, we have found that the time TPN is started is important in influencing the course of the disease and in the development of local complications, as well as in the mortality rate. Patients whose TPN was started within the first 72 hours of the disease had a 23.6% complication rate and 13% mortality, in comparison with patients whose TPN was started later in the course of the disease, who had a 95.6% complication rate (p less than 0.01) and a mortality rate of 38% (p less than 0.03). The nutritional status of the patients during TPN administration of 28.4 days was maintained either steady or was improved, as assessed by nitrogen balance, serum levels of transferrin (p less than 0.05), and albumin (p less than 0.05). The administration of fat solution, either to prevent essential fatty acid deficiency or to provide part of the caloric requirements, was found to cause neither clinical nor laboratory worsening of the disease. All pancreatic fistulae that developed during the course of the disease spontaneously closed in patients receiving TPN without operation in a mean period of 33.3 days, and all pseudocysts subsided in an average of 18.3 days. Those who died (overall mortality rate 24%) had had uncontrollable sepsis, which resulted in hypercatabolism and multiple system organ failure.(ABSTRACT TRUNCATED AT 250 WORDS)