The effects of the neuroprotective aminosteroid U74389G were monitored microdialytically in rat cortex during 4 h after permanent middle cerebral artery occlusion. Either U74389G or vehicle only was administered one hour before and 2 h after operation. The dialysate was analysed for on-line pH, ascorbic acid, uric acid, glucose and lactate. In aminosteroid treated animals the levels of ascorbic and uric acids were lower in dialysates after occlusion, total release of lactate was significantly reduced and on-line pH was significantly higher than in control animals. Lesion volume at 4 h, which was significantly reduced in treated animals, correlated positively with ascorbic acid release and on-line pH. Results suggest that neuroprotective effects of aminosteroids might be explained by: (a) preservation of intracellular levels of the radical scavenger ascorbic acid with possible concomitant reduction of glutamate release; and (b) reduced lactate release and increased pH which might influence oedema positively. Copyright 1999 Harcourt Publishers Ltd.