The obese (C57BL/6J ob/ob) mouse is a commonly used animal model of non-insulin-dependent diabetes mellitus. It has recently been demonstrated that this mouse is not consistently hyperglycemic, however, unless it is subjected to environmental stress. In the present study, hyperglycemia in obese mice was induced by classical conditioning. Obese diabetic mice and lean control animals were exposed to shaking stress. All animals developed hyperglycemia in response to shaking. To demonstrate classical conditioning, some obese and lean animals were exposed to a metronome prior to and during the shaking. Other animals were exposed to the metronome and shaking in a noncontingent fashion and one group of animals was exposed to the metronome without any exposure to shaking. All animals received seven exposures to one of the three above conditions over a 3-day period. On the 4th day all animals were exposed to the metronome alone, following which blood samples were drawn. Classical conditioning of stress hyperglycemia was demonstrated in obese, but not in lean, mice.