The direct effects of theophylline and enprofylline, a new anti-asthma xanthine derivative without adenosine receptor blocking action, were studied in the isolated, spontaneously beating rabbit heart. At increasing concentrations from 2 x 10(-5)-5 x 10(-4) M both drugs produced increases in heart rate up to 143% and 162% and in contractility up to 135% and 147% from control values (100%), respectively. At concentrations higher than 10(-3) M contractures and heart block occured. Enprofylline showed a potency about 2.3 times higher than theophylline. Coronary flowrate did not increase. Myocardial oxygen consumption was moderately increased by the drugs. The myocardial pharmacokinetics showed two-compartment characteristics for both drugs. Half-times of the two phases of accumulation were for theophylline 0.28 and 0.98 min. and for enprofylline 0.31 and 0.78 min. The terminal disposition half-time for enprofylline was, however, 2.7 times higher than that of 0.91 min. for theophylline, apparently due to a stronger binding of the former drug intracellularly. Both xanthines accumulated against a concentration gradient showing myocardial tissue-perfusion liquid ratios of about 2.9 for theophylline and 3.7 for enprofylline. The drugs seem to exert their primary action on sarcolemmal binding sites which probably are unrelated to adenosine receptors.