An average 2.2-fold increase in the peak plasma concentrations of the non-steroidal anti-inflammatory agent diftalone in the presence of food was observed in three studies carried out with healthy volunteers who received an oral dose of 0.75 g (6 subjects, study 1), 0.25 g (10 subjects, study II) and 0.5 g (6 subjects, study V) of the compound at 9:00 a.m. both in fasting conditions and after a meal. The effect does not depend on the unusual time (8:00 a.m., selected for experimental needs) at which the subjects were given the meal. In fact, a 2.5-fold increase in plasma concentrations was observed when an oral dose of 0.75 g of diftalone was administered to 2 subjects (study II) both at 8:00 a.m. in fasting conditions and at 1:00 p.m. after a meal. A similar enhancement in the absorption of diftalone was observed when 5 healthy volunteers (study VI) received an oral dose of 0.5 g of the compound both as plain capsules and as capsules containing dry ox bile. However, the absorption of diftalone was not modified when the compound was administered orally as an aqueous suspension or in tensioactive vehicles, or after 20 mg of metoclopramide (study II). Also, the results of a study (IV) on 2 subjects partly deprived of bile after surgery, showed that diftalone does not undergo enterohepatic circulation. The hypothesis that the increase in diftalone absorption is mainly due to bile flow following food intake is supported by all the above experimental results.