Beta agonists such as isoproterenol are widely used in the treatment of acute asthmatic attacks. It would not be unexpected that some patients receiving isoproterenol might have ingested caffeine as an over‐the‐counter drug or beverage. This study explores the possible interaction between these two drugs. Anesthetized mini pigs were injected with 0.5 mg/kg caffeine iv followed by a 10‐min infusion of 1 μg/kg·min isoproterenol. Heart rate, EKG, respiration, and blood pressure were recorded continuously and the animals were sacrificed at 72 h. The two drugs in combination produced subtle changes in heart rate and blood pressure with significant alteration in the EKG tracing (premature ventricular contractions and extrasystoles). These changes persisted for 8 to 24 h. At autopsy both gross and microscopic lesions were noted in 10 of the 13 minipig hearts receiving the combination of drugs. This was not true of the six minipigs given only caffeine or the eight minipigs receiving only the infusion of isoproterenol. No changes in EKG tracings or pathologies were noted with caffeine and only two of eight animals infused with isoproterenol showed any lesions.