Many important crystalline solids cannot be prepared in the form of single crystals of sufficient size and quality for single-crystal X-ray diffraction studies, and in such cases it is essential that structural information can be extracted from powder diffraction data. In this paper, a method employing a Monte Carlo algorithm for crystal structure determination from powder diffraction data is developed and applied. In this method, a series of structural models is generated by random movement of a collection of atoms within the unit cell, and the acceptance or rejection of each trial structure is based upon the Metropolis importance sampling technique-in employing this technique, the agreement between the experimental powder diffraction pattern and the powder diffraction pattern calculated for the structural model is considered. The success of this method for ab initio crystal structure determination from powder X-ray diffraction data is demonstrated by its application to determine the known crystal structure of p-CH3C6H4SO2NHNH2 and the previously unknown crystal structure of p-BrC6H4CH2CO2H. In view of the successful application of the methodology reported here, we predict that this Monte Carlo technique will have an important future role in ab initio crystal structure determination from powder diffraction data.