Bönisch et al. (1974) identified kinetically two extraneuronal compartments into which 3H-isoprenaline distributes in the perfused rat heart: compartment III (characterized by a half time for the efflux of 3H-isoprenaline of about 10 min) had about the same size as compartment IV (half time for efflux: 23 min). These authors suggested that compartment III might be located in the vascular smooth muscle, while compartment IV might be located in myocardial cells. The present study was carried out to validate or refute this suggestion. Rat hearts were perfused for 5, 20 or 60 min with 1 mumol/l 3H-isoprenaline; additional hearts were perfused with 1 mumol/l 3H-isoprenaline for 30 min in the presence of either 20 mumol/l corticosterone or 20 mumol/l corticosterone plus 30 mumol/l cocaine. COMT was inhibited in all experiments (by the presence of 100 mumol/l U-0521). Quantitative autoradiography revealed in all groups that the silver grain density (grains/mm2) was greater over small blood vessels (arterioles and venules) than over myocardial cells. However, total silver grains over myocardial cells greatly exceeded those over small blood vessels (by a factor of 6 to 9). Thus, the suggestion of Bönisch et al. (1974) is untenable. Autoradiographic results obtained with small specimens of ventricular muscle are representative of the whole heart, since "silver grains over total tissue" (per mm2) were highly significantly correlated with the 3H-isoprenaline content of the homogenized hearts (in pmol/g). While corticosterone reduced the accumulation of 3H-isoprenaline in myocardial cells, it failed to affect the appearance of silver grains over Purkinje cells. However, cocaine prevented this type of accumulation. Thus, uptake in Purkinje cells appears to resemble neuronal rather than extraneuronal uptake.