The differentiation of closely related compounds is a subject of considerable forensic importance, especially for drugs where relatively minor compositional or structural variations, such as different substituents of isomerism, have considerable physiological effects and may distinguish between a controlled substance and an uncontrolled one. Frequently, common techniques such as ultraviolet (UV) spectroscopy are ineffective in such cases, and others such as thin-layer chromatography (TLC) lack specificity of response. Some effective techniques such as mass spectrometry (MS) are often not readily available. In this study, the use of powder X-ray diffraction (XRD) in a situation of this type is explored. X-ray powder diffraction patterns of microgram quantities of drugs can be satisfactorily recorded with a Gandolfi camera. Despite the chemical similarity of the drugs investigated, the XRD powder patterns of the present study differed substantially enough to make visual comparisons adequate to distinguish among them; this implies that the micro-XRD powder patterns can be useful in establishing identity of drugs in more general cases. Because of its ready availability and relatively inexpensive operation, powder XRD compares well with MS methods of drug analysis for samples as small as microgram quantities.