The aim of this study was to determine the mechanism of transport of 3-deazaguanine in the rat heart. We used single-pass, paired-tracer dilution method on isolated and retrogradely perfused rat hearts. The maximal cellular uptake (Umax) and total cellular uptake (Utot) of 3-deazaguanine were determined under control conditions and under influence of possible modifiers. Both Umax and Utot were significantly reduced in the presence of unlabeled 3-deazaguanine (from 19.57 +/- 2.02% to 8.14 +/- 1.19% and from 16.49 +/- 3.65% to 4.70 +/- 1.96%, n=6, respectively). The presence of pyrimidine nucleoside thymidine caused the reduction of both Umax and Utot (from 20.03 +/- 3.76% to 13.58 +/- 3.16% and from 16.43 +/- 3.58% to 11.94 +/- 3.13%, n=6, respectively). Also, we tested the effect of the absence of sodium ions in perfusion solution (both Umax and Utot, significantly reduced from 17.95 +/- 2.73% to 16.67 +/- 2.16% and from 16.68 +/- 2.97% to 14.81 +/- 3.04%, n=6, respectively) and the effect of dinitrophenol (both Umax and Utot significantly reduced from 19.09 +/- 3.68% to 10.58 +/- 3.14% and from 16.86 +/- 3.84% to 7.10 +/- 3.11%, n=6, respectively). The results of self- and cross-inhibition studies show that the transport of 3-deazaguanine is saturable, energy- and sodium-dependent and that 3-deazaguanine uses endogenous transport systems for thymidine and adenosine for its own transport.