The transient effect of surfactant therapy that is observed in some patients might, at least in part, be explained by a nonhomogeneous distribution. Therefore, we investigated the distribution of a surfactant preparation (Alvofact, 45 g/L) that is used clinically. Rabbits with severe respiratory failure were treated with this surfactant at a dose of 100 mg/kg body weight, and the distribution of surfactant was determined by the use of 141Ce-labeled microspheres that were mixed with the surfactant. Fifteen min after surfactant administration, the rabbits were killed, and the lungs were removed and divided into 200 pieces. The radioactivity per mg lung tissue was determined in each piece. We found that the endotracheal instillation of this surfactant preparation results in a nonhomogeneous distribution. However, a significantly improved distribution was obtained when this dose of surfactant (100 mg/kg body weight) was diluted with normal saline to a concentration of 6.25 g/L. The consequence of the administration of this dose was an intratracheal fluid administration of 16.0 mL/kg body weight. The distribution was also nonhomogeneous after the administration of a small-volume (2.4 mL/kg body weight), low-concentration surfactant preparation (6.25 g/L). We conclude that a surfactant preparation with clinical application is distributed nonhomogeneously in the lungs after endotracheal administration. The distribution can be significantly improved by increasing the fluid volume in which the surfactant is suspended.