The abuse of new psychoactive substances (NPS) has been dramatically increasing all around the world since the late 2000s. The availability of hundreds of NPS in the past decade is challenging for both public health and global drug policies. We present the intoxication of two subjects who had sniffed a white creamy powder, characterized as 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine]. Plasma samples were analyzed by ultra-high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). Concentrations of 25I-NBOMe were 37 and 72ng/mL, respectively. Major impairment of both subjects, including visual hallucinations and alteration of behaviour were attributed to these high concentrations. The data were compared to the few reports available in the medical literature.