The combined effects of microwave radiation and some drugs were studied in an isolated frog auricle preparation. The experiments established that exposure to pulse-modulated 915 MHz microwaves for up to 40 min had no effect on either the rate or the amplitude of spontaneous auricle twitches, unless the average absorbed power was high enough to produce preparation heating. Treatment of the preparation with saline containing (0.6-3.0) 10(-5) M of propranolol or (0.5-1.5) 10(-7) M of atropine altered neither its pacemaker nor its contractile functions; these drugs also had no effect when they were combined with nonthermal microwave irradiation. Caffeine (1 mM) strongly increased the average heart power, which was calculated as the product of twitch rate and amplitude. The caffeine effect appeared to be significantly augmented (by about 15%, P < 0.02) under exposure to burst-type pulsed microwaves (pulse width, 1.5 msec; pause, 2.5 msec; 8 pulses/burst, 16 bursts/s; average SAR, 8-10 W/kg). By itself, this modulation was not effective; the heating of the preparation and saline during exposure was approximately 0.1 degrees C, which could not account for the detected changes. The experimental results demonstrate that caffeine treatment increases the microwave sensitivity of the frog auricle preparation and reveals primarily subthreshold, nonthermal microwave effect.