Assuming that acidic degradation of lipase was the major cause of failure for the correction of steatorrhea by pancreatic extracts, we compared the in vitro and in vivo activities of a fungal lipase (FL) (Rhizopus arrhizus) with classical porcine pancreatic extract (Eurobiol). The choice of FL was determined by its two optimum pH (3.5 and 7.4). Five factors known to modify lipase activity were tested: pH, biliary acids colipase, trypsin and albumin. Bioavailability was measured by using a double intubation method in 13 patients with severe pancreatic insufficiency. Each enzymatic preparation was given during a test meal in a randomized and cross-over fashion. Results of the in vitro study showed that FL differed from pancreatic lipase by the following properties: better resistance in acidic solution, inhibition by biliary salts, absence of effect of colipase and rapid degradation by trypsin. In vivo the percentage of lipase activity recovered was 14.2 +/- 10.6 p. 100 for FL and 56 +/- 50 p. 100 for the classical pancreatic preparation. Compared with placebo significant differences in the recovery rate of lipolytic activity were observed with the pancreatic preparation only and started at the 40th min after the end of the test meal. These results showed that lack of degradation in acidic milieu is not the only valuable criterion for the choice of an efficient lipase preparation. The role of other potential factors such as gastric emptying as well as proteolytic degradation of the enzyme should be considered as well.