Advancing (theta(A)) and receding (theta(R)) contact angles were measured with several probe liquids on the external facets (201), (001), (011), and (110) of macroscopic form I paracetamol crystals as well as the cleaved (internal) facet (0 10). For the external crystal facets, dispersive surface energies gamma(d) calculated from the contact angles were found to be similar (34 +/- 1 mJ/m(2)), while the polar components varied significantly. Cleaving the crystals exposed a more apolar (010) surface with very different surface properties, including gamma(d) = 45 +/- 1 mJ/m(2). The relative surface polarity (gamma(p)/gamma) of the facets in decreasing order was (001) > (011) > (201) > (110) > (010), which agreed with the fraction of exposed polar hydroxyl groups as determined from C and O 1s X-ray photoelectron spectroscopy (XPS) spectra, and could be correlated with the number of non-hydrogen-bonded hydroxyl groups per unit area present for each crystal facet, based on the known crystal structures. In conclusion, all facets of form I paracetamol crystals examined exhibited anisotropic wetting behavior and surface energetics that correlated to the presence of surface hydroxyl groups.