The interaction of diclofenac as a pure substance was investigated without and with concomitant administration of food in 8 healthy, male volunteers (age: 23-29 years, body weight: 60-87 kg). Diclofenac was given as a pure substance by means of a rapid dissolving capsule in a dose of 50 mg. Paracetamol (1.5 g), a marker of gastric emptying rate, was administered simultaneously with diclofenac in order to elucidate the influence of gastric emptying rate on diclofenac absorption. The bioavailability was determined according to the time (tmax) of the concentration maximum in plasma (Cmax) and the area under the curve (AUC). Food significantly delays tmax of diclofenac (without food: [mean +/- SD] 0.8 +/- 0.5 h, range: 0.5 +/- 2 h; with food: 2.4 +/- 0.9 h, range: 1.5-4 h) and diminishes Cmax (without food: 1,125 +/- 765 ng/ml, range: 95-2,100 ng/ml; with food: 434 +/- 151 ng/ml, range: 250-555 ng/ml). The AUC is not influenced (without food: 1,217 +/- 368 ng/ml x h; with food: 1,037 +/- 267 ng/ml x h). The bioavailability of paracetamol is unchanged. It is concluded that the diminishing of Cmax and the delay of tmax of diclofenac are possibly the consequence of an interaction with food and not of the delayed gastric emptying per se.