Current growth hormone (GH) therapy with daily subcutaneous injections results in elevated serum concentrations of GH lasting for several hours, whereas physiologic GH secretion is characterized by a short-duration peak and low basal concentrations. A closer imitation of this pattern might be achieved by administering GH nasally. We studied the effect on the absorption of nasally administered human GH of increasing concentrations of the enhancer didecanoyl-L-alpha-phosphatidylcholine (DDPC). Four formulations of nasal GH containing the enhancer DDPC in the relative concentrations 0, 4, 8, and 16% w/w were administered in random order. Participants were admitted to the hospital during the four study periods. On four occasions the subjects received GH 6 IU (2 mg) in each nostril. Blood was sampled frequently for four hours. Anterior rhinoscopy was performed at 0 and 4 h. During the study the subjects completed a questionnaire to record nasal symptoms. Sixteen healthy subjects were examined at 0800 h after an overnight fast. Bioavailability of a nasal preparation of human GH: area under the curve (AUC), the maximum concentration (Cmax), and the time to reach maximum concentration (tmax). Scores for each nasal symptom were recorded as were the total scores. AUC, Cmax, and tmax were not significantly affected by increasing the DDPC concentration from 0 to 4 percent or from 8 to 16 percent. AUC and Cmax, however, increased significantly when the concentration of DDPC was changed from 4 to 8 percent. Mean (+/- SD) AUC (microgram.h/L) increased from 20.51 +/- 10.53 (4 percent) to 46.14 +/- 34.59 (8 percent), (p < 0.005). Mean (+/- SD) of Cmax (microgram/L) increased from 11.11 +/- 5.02 (4 percent) to 28.22 +/- 20.85 (8 percent), (p = 0.002). Mean (+/- SD) of tmax (min) was not significantly different on the four occasions (range 40.6 +/- 36.4 to 61.0 +/- 45.2 min, p = 0.13). The symptom scores (range 17.56-21.5, maximum 360) were not significantly different (p = 0.59). Increasing the relative concentration of the enhancer DDPC increases the absorption of nasally administered GH.