Leptin is a peptide hormone produced by adipocytes which provides a negative feedback signal to control the amount of body fat. The action of leptin on food intake and weight loss is thought to be mediated by interaction with its hypothalamic receptor. We examined the biodistribution and brain uptake of radioiodinated leptin (123I-leptin) by dynamic gamma imaging in six anaesthetized New Zealand white rabbits. Leptin uptake was seen in the brain, lungs, liver and kidneys. In the brain, increase in radioactivity as a function of time was seen in the choroid plexus area. The choroid plexus to brain radioactivity ratio (CP/BR) was used as the target to background ratio. The CP/BR ratio increased up to approximately 40-60 min, after which a steady state in CP/BR was achieved. The steady state uptake ratio was higher in the rabbits that had fasted for only 6-8 h before the experiment (CP/BR approximately 2.5) than in those that had fasted for 25-27 h before the experiment (CP/BR approximately 1.8). Thus, leptin uptake in vivo occurs in the choroid plexus region of the brain and in the lungs, kidney and the liver. The uptake of leptin in the choroid plexus appears to be saturable, as indicated by the achieved steady state in the CP/BR radioactivity curve 40-60 min following 123I-leptin injection. The lower steady state CP/BR after prolonged fasting may be the result of the downregulation of leptin receptors in the choroid plexus.