This study on the pharmacokinetics of antibiotics in nasal secretions was carried out with two orally applicable penicillin derivatives which show different resorption patterns. Each of the antibiotics (Ampicillin and Bacampicillin) was given in equimolar doses to 20 healthy young volunteers, with normal mucosa, in a double blind cross over fashion. Nasal secretions were collected 1, 2, 3, 4, 6, and 8 h after the application of a single dose to the overnight fasted persons. In 10 of them blood was taken at 0.5, 1, 1.5, 2, 3, and 4 h after the administration. For the sampling of the nasal secretions cotton wool was weighed together with an airtight vial containing 300 microliter of phosphate buffered saline (PBS). The dry cotton wool stayed in the nasal cavity for 20 min, was then put into the PBS and weighed again. The difference determines the amount of secretions collected. After 30 min the soaked cotton wool was pressed out into a vial with a sterile syringe. One hundred microliters of this solution was taken to determine the antibiotic concentration by a micromodification of the agar diffusion technique. In the remaining fluid total protein and albumin were quantitatively determined. The amount of nasal secretions which have been collected are, on average, independent of the time (Fig. 1). With rising secretion the protein content decreases (Fig. 5) as is the case with the albumin concentration. Regarding all persons, the protein content and albumin (Fig. 4) remain constant during the experiment from 8 a.m. to 4 p.m. The differences between the values shown in the figures are not significant. Comparing the mean concentration for the antibiotic at different times after the application, it is obvious that the agents show different curves (Fig. 6). With ampicillin the maximum of 0.13 microgram/ml is reached at 2 h after the administration whereas with becampicillin the maximum of 0.84 microgram/ml is reached after 1 h. The concentrations in the nasal secretions are clearly dependent of the serum values. In the serum the maximum of the mean values plotted against the time of 2.7 microgram/ml is to be found at 2 h, if ampicillin is given, whereas the maximum of 9.3 microgram/ml is reached at 1 h after bacampicillin administration. In both cases in serum and nasal secretions the mean concentration maximum is about three times higher after bacampicillin as compared with ampicillin. As a reference for the concentration of the antibiotic the total protein content of the sample is more suitable as compared with sample volume and albumin because of its easy and exact determination. The results show that the nasal secretions can be used as a model to evaluate the pharmacokinetics in the mucosa of the upper respiratory tract if an adequate number of test persons is used.