The anisotropy of acetaminophen hardness was demonstrated using both Vickers and Knoop indentation hardness measurements. Based on a model of Knoop hardness anisotropy proposed by Brookes et al. (1), it was concluded that plastic flow in acetaminophen crystals occurs primarily as a result of slip in the (010)<001> system. This conclusion was corroborated with the results of the Vickers indentation tests. The apparent brittleness of acetaminophen was rationalized because only one slip system appeared to be operative. Under these conditions generalized plastic flow cannot occur, since this requires the operation of at least five independent slip systems (2). The high stress concentrations that result from flow lead to fracture. Therefore acetaminophen is more precisely classified as being semiductile. When a material deforms plastically as a result of slip in only one slip system, considerable crystal realignment can occur during compaction. This in turn can facilitate capping during decompression and ejection, since the cleavage plane, (010), would become aligned with the direction of highest tensile stress.