To study the variability of the fraction of CPK released from the infarcted heart which enters the serum (serum entry ratio, or SER) with size and model of infarction, nine dogs underwent homogeneous infarctions (LAD ligation) of varying sizes, and 10 dogs underwent scattered infarctions (left coronary embolization). In homogeneous infarcts there was an inverse linear relationship of SER to infarct size (IS) (SER = -0.8514% LV + 0.345, r = 0.98). No such relationship was found for scattered infarcts. CPK Kd (exponential disappearance constant for CPK) was not significantly different in homogeneous (-0.00178 min-1) vs scattered infarcts (-0.00195 min-1). Although similar IS was produced in each (homogeneous 19.9% LV, scattered 18.4% LV) cumulative CPK serum entry (CPKr) was much lower in homogeneous (4175 mlU/ml) vs scattered infarcts (7,296 mlU/ml). SER was also much lower in homogeneous (17.7%) vs scattered infarcts (29.0%) (P less than 0.025). Cumulative CPK plateau occurred significantly later in homogeneous (15.8 hours) vs scattered infarcts (11.7 hours) (P less than 0.01). Further corrections to the serial CPK equations for IS determination are indicated. The method may not be applicable in some infarct situations, e.g., scattered infarction.