In a previous study we found two agents, the α 2 ‐agonist medetomidine ((±)‐4‐[1‐(2,3‐dimethylphenyl)ethyl]‐1 H ‐imidazole) and the α 2 ‐agonist clonidine (2‐(2,6‐dichloroanilino)‐2‐imidazoline), that specifically and efficiently impede settlement of the barnacle Balanus improvisus , one of the most serious biofouling organisms in Swedish waters. Medetomidine, but not clonidine, is known to adsorb to solid polystyrene (PS) surfaces in the presence of salt, a feature that is of particular interest in attempts to develop an efficient antifouling surface. We show that medetomidine, but not clonidine, has a significant ability to adsorb to untreated (hydrophobic) PS in two different incubation media: filtered seawater (FSW) and deionized water (mQ). At negatively charged (hydrophilic) PS, medetomidine displays a strong interaction with the surface in both incubation media. At the hydrophilic PS, clonidine also displays a significant interaction with the surface when incubated in mQ and a weaker, but not significant, interaction when incubated in FSW. By studying the effects of time, incubation media, and pH on the adsorption of medetomidine and clonidine, we suggest that medetomidine is associated to hydrophobic PS by means of hydrophobic interactions, while the adsorption of medetomidine and clonidine to hydrophilic PS contains elements of electrostatic interaction. Using time‐of‐flight secondary ion mass spectroscopy (TOF‐SIMS) we detected only weak signals from medetomidine on the hydrophobic PS surfaces, while strong medetomidine signals were observed on hydrophilic PS. This suggests that the adsorbed medetomidine, to a greater extent, desorbed from the hydrophobic rather than from the hydrophilic PS surfaces during exposure to vacuum. The strong surface affinity of medetomidine on both types of surfaces and the preserved antifouling activity are valuable features in designing a marine coating.