The mechanisms underlying olanzapine-induced weight gain have not yet been fully elucidated. To examine the effects of long-term treatment with olanzapine on different aspects of energy balance, we administered olanzapine to male rats. Osmotic minipumps were chosen as preferred mode of administration because the half-life of olanzapine is only 2(1/2) h in rats compared to 30 h in humans. We discovered that, within one week, degradation of olanzapine occurred in the solution used to fill the minipump reservoir. This resulted in a decrease in delivered olanzapine and declining plasma levels over the course of the experiment. Therefore, we caution other researchers for the limitations of using osmotic minipumps to administer olanzapine for longer periods of time.