Summary. In the 1960s, pioneering studies of Abendroth with Henrich; Paulsen; and Schmitz with Ohme showed that diazirines could form reactive carbenes upon heating or exposure to light. Since then, diazirines became useful labels in photoaffinity studies of bioactive compounds. Especially popular today are dialkyl diazirines and trifluoromethyl aromatic diazirines (types A, B in Figure ). Herein, we prepared the previously unknown difluoromethyl-and the previously neglected trifluoromethylaliphatic diazirines (types C, D in Figure ), and comprehensively characterized them. Model photolabeling experiments and biological studies indicated that trifluoromethyl aliphatic diazirines could indeed be used as photoaffinity labels. At the same time, the difluoromethyl aliphatic diazirines were chemically labile due to C-F bond solvolysis.