Cryogenic milling could reduce the ductility in the milling operations of semi-brittle and relatively ductile pharmaceutical particles. However, to achieve a better application of this technology, it is necessary to establish the relationship between the influence of temperature on the mechanical properties and breakage characteristics of the single particle and the bulk crushing behavior of these types of material. The focus of this paper is on the analysis of bulk crushing behavior of alpha-lactose monohydrate particles in response to temperature variations, based on single particle mechanical properties and side crushing strength at different temperatures and the use of distinct element analysis. The effect of temperature on the side crushing strength of the particles has been quantified by quasi-static side crushing tests. The experimental results show a significant increase in the strength of the single particles by decreasing the temperature. These results are used in the distinct element analysis to simulate the bulk crushing behavior of pharmaceutical particles as affected by the temperature. The predictions are compared with the experimental results, for which a reasonable agreement is found for the ambient temperature case. There are some differences for the case of -20degreesC, due to lack of reliable data for Young's modulus.