The purpose of this study was first to develop an animal model for stress-induced digitalis toxicity in such a way that physical and psychological factors might be kept separate. The other purpose was to begin an analysis of the mechanism of this psychosomatic effect. To do this, free-ranging guinea pigs were subjected to repeated sessions of signaled shock (Pavlovian fear conditioning) or to signal alone. On a probe day in which signals were delivered as usual but shock was not administered, guinea pigs were infused i.v. with ouabain after an i.p. injection of either saline, atropine sulfate or atropine methylbromide. Saline-treated guinea pigs with prior fear conditioning became digitalis toxic at a significantly lower dose of the drug than control guinea pigs that had not had exposure to signaled shock. This effect was blocked by both atropine salts, indicating a cholinergic effector on the blood side of the blood-brain barrier responsible for early arrhythmogenesis in the fear-conditioned animals.