Propofol depresses both cerebral oxygen consumption and glucose utilization. We tested the hypothesis that these well described effects on brain metabolism are manifest by a reduction in neuronal acid production in vitro. The rate of extracellular acidification in primary cell cultures of rat cortical neurones was measured using a novel instrument (silicon microphysiometer) after stimulation with propofol 0.3, 3 and 30 mu g ml(-1). Intralipid 10% served as a control. Propofol 3 mu g ml(-1) caused a mean decrease of 1.51 (SEM 0.71)% in baseline acidification rate, which was significantly greater than that produced by 0.3 mu g ml(-1) or Intralipid alone (P<0.05). The reduction after stimulation with propofol 30 mu g ml(-1) was 4.68 (0.35)% of baseline rates and this in turn was significantly greater than that elicited by propofol 3 or 0.3 mu g ml(-1), or Intralipid (P<0.001). We have confirmed the depressant effect of propofol on cerebral metabolism and established that propofol inhibits neuronal acid excretion in vitro.