Exposure to an open field is psychologically stressful and leads to an elevation in core temperature (T(c)). Methyl scopolamine (MS), a muscarinic antagonist, and pyridostigmine (PYR), a carbamate that inhibits acetylcholinesterase, do not cross the blood-brain barrier and have little effect on T(c) in resting, nonstressed animals. However, we have found that MS has an antipyretic effect on T(c) that is caused by handling and cage-switch stress. PYR should act pharmacologically to reverse the effects of MS. To this end, we assessed the effects of MS and PYR on stress-induced hyperthermia. Male Sprague-Dawley rats at 90 days of age were housed individually at an ambient temperature of 22 degrees C. T(c) and motor activity were monitored by radiotelemetry in an open-field chamber. Rats were dosed intraperitoneally at 1200 with 1.0 mg/kg MS, 0.1 mg/kg PYR, a combination of MS and PYR, or saline and placed immediately inside the open-field chamber for 60 min. Stress-induced hyperthermia was suppressed immediately by MS and enhanced by PYR. T(c) only increased by 0.3 degrees C in the MS-treated animals. The hyperthermic response in the PYR group was nearly 0.6 degrees C above that of rats dosed with saline. Coadministration of PYR and MS led to a stress-induced hyperthermia response nearly identical to that of rats injected with saline. Overall, open-field stress exacerbated the effects of MS and PYR on body T(c) and provides support for a peripheral cholinergic mechanism that mediates stress-induced hyperthermia.