Accumulation of lactate in myocardial cells has been proposed as a primary trigger of ischemic damage in heart. This hypothesis was tested using isolated cardiac myocytes from adult rats. Cells were subjected to anoxia/reoxygenation protocols in the presence or absence of lactate at two extracellular pH values. Reductions in total rods and increased numbers of shortened rods ("contracted" cells) were evident in cell populations exposed to anoxia and in reoxygenated populations in the absence of glucose at pH values of 6.9 and 7.3. Although lower pH reduced cell adenine nucleotide contents over those seen at higher pH, neither 10 mM nor 50 mM lactate enhanced nucleotide loss or caused extra morphological damage under any condition in this study. Therefore, under conditions simulating those in ischemic heart, cell damage could not be attributed to high lactate concentrations.