A dry powder aerosol formed of human growth hormone (hGH), lactose and dipalmitoylphosphatidylcholine was assessed for systemic delivery of the hormone in rats. The fate of the protein locally in the deep lung was examined post-delivery. The powder was prepared by spray-drying and presented a primary particle diameter of 4.4 microm and a tap density of 0.069 g/cm(3). The mass median aerodynamic diameter was 4.4 micron in the multi-stage liquid impinger at 60 l/min using a Spinhaler device. The emitted dose and fine particle fraction were 89% and 58%, respectively. Varying the airflow rate from 30 to 90 l/min had limited impact on aerosolization properties in vitro. No hGH dimers or glycation adducts were produced during formulation of the powder. hGH absorbed into the bloodstream with a time to peak of 23 and 52 min and with an absolute bioavailability of 23% and 8% following intratracheal insufflation of the dry powder and intratracheal spray-instillation of a solution of the hormone, respectively. Confocal imaging of rat lung revealed an intense uptake of fluorescein isothiocyanate (FITC)-hGH by alveolar macrophages as early as 1 h post-delivery. A dry powder aerosol made of selected GRAS excipients improved absorption of hGH from the lung over a simple solution.