The incubation of isolated hepatocytes with 10-100 microM cadmium (Cd) decreased the ATP/ADP-ratio, the ATP/AMP-ratio and the adenylate energy charge and enhanced the lactate/pyruvate-ratio in a time- and concentration-dependent manner. Likewise, the cellular oxygen-consumption was decreased at early incubation times, when the cell membrane was still intact, as judged by the Trypan Blue-exclusion test. Similarly, Cd-concentrations above 0.3 nmol/mg mitochondrial protein inhibited the succinate- and malate/pyruvate-stimulated respiration of isolated mitochondria. This critical concentration was also reached in mitochondria of hepatocytes, when exposed to 25 microM Cd for less than 30 min. We therefore suggest that the inhibition of cellular respiration and the breakdown of cellular energy generation is mediated by a severe disturbance of mitochondrial respiratory functions due to Cd. This effect seems to be an early event in Cd-toxicity in isolated hepatocytes.