To define binding characteristics of drugs, levodopa melanin was prepared with the aid of mushroom tyrosinase. The binding of radiolabeled substances was studied with increasing concentrations of melanin in a fixed volume of potassium phosphate buffer (pH 7.4) at 37 degrees. The affinity and capacity of the drug binding were calculated according to Langmuir's adsorption isotherm. The affinity constant of various sympathomimetic amines such as (-)-amphetamine, (+)-amphetamine, (-)-ephedrine, (+/-)-octopamine, and (+)-norepinephrine ranged from 1.1 to 2.8 X 10(5) M-1. The binding capacity for the amines ranged from 1.4 to 3.2 X 10(-9) mole/mg. Although the capacity of (+/-)-cocaine for binding was similar to that of the amines, the affinity was slightly higher, 8.9 X 10(5) M-1. The binding of atropine to the synthetic melanin appeared to be a saturable process with the affinity and capacity values of 0.2 X 10(5) M-1 and 7.6 X 10(-9) mole/mg, respectively. Although the binding lacks stereoselectivity, the drugs vary in their capacity and affinity to bind with melanin. The observed differential pharmacological and toxicologic properties of drugs in the pigmented tissues may in part be related to their differential bi binding characteristics.