An automated method measuring cardiac myocyte surface area was described and used as an index of cell growth. Hearts from 2 to 4 day old rats were digested through incubation in cold trypsin solution. Cells were cultured in M199 supplemented with 1% serum, 10% serum, or 10% serum plus 10(-7) molar norepinephrine. One to 4 days after plating, cells were fixed and stained for image analysis and morphometric assessment. The enhanced image of stained heart cells was digitized for calculation of perimeter, length, width, and area. Areas of individual myocytes varied widely, with the distribution skewed toward larger cells. The standard deviation increased proportionally with mean cell area. Logarithmic transformation of the data yielded normalization and a more homogeneous variance. The geometric mean area of heart cells supplemented with 1% serum increased slightly but significantly during 4 days in culture, while that of cells supplemented with 10% serum increased nearly four fold. Supplementing cells with norepinephrine plus 10% serum did not induce further size increases. The authors conclude that the technique can rapidly and objectively chart the growth of heart cells after pharmacological or toxicological treatment.