A 65-year-old woman with chronic pain was admitted to the hospital for severe recurrent major depression complicating Parkinson's disease (PD). Pain complaints were closely related to the fluctuating motor syndrome of PD. Specifically, pain was experienced in conjunction with hypomobility, and, as a result, she self-medicated with extra carbidopa/levodopa. A regimen of tramadol and cyclobenzaprine, along with sustained-release carbidopa/levodopa for PD and buproprion for her depression resulted in sustained symptomatic and functional improvement. Craving for, and self-medication with, supplemental carbidopa/levodopa ceased. Theoretical support for synergism among dopamine and opioid neurotransmitter systems can be found in recent literature.