The metabolism of second order auditory neurons in nucleus magnocellularis (NM) in the chick brainstem can be profoundly altered when excitatory input from the cochlea is removed. Within hours of cochlea removal, NM neurons show an increase in histochemical staining for the Kreb's cycle enzyme succinate dehydrogenase (SDH), followed in several days by decreases in SDH staining. We examined the activity of another Kreb's cycle enzyme, malate dehydrogenase (MDH) using a histochemical stain and a sensitive quantitative biochemical assay for comparison. We found changes in MDH staining similar in time course and magnitude to those of SDH; within 4 h of cochlea removal, MDH activity increases in ipsilateral NM neurons. By 9 days after cochlea removal MDH activity decreases, although not to the same degree as seen with SDH. Biochemical measurements of MDH activity also showed an early increase in activity in ipsilateral NM, followed at 9 days survival by a decrease in activity. Biochemical measurements of the activity of other enzymes in NM may be useful in further defining the metabolic consequences of deafferentation.