We investigated the effect of mild (34 degrees C) postischemic hypothermia on hippocampal neuronal damage in 43 rats as a function of the duration of forebrain ischemia. Two temperatures and two durations were investigated. In two normothermic groups ischemia lasted 8 (n = 15) and 12 (n = 10) minutes, respectively. In two hypothermic groups ischemia lasted 8 (n = 9) and 12 (n = 9) minutes, respectively, and was followed immediately by the lowering and maintenance of rectal temperature to 34 degrees C for 2 hours. Seven days after the ischemic insult, the rats were sacrificed and the brains were prepared for histologic analysis; the percentage of necrotic neurons among the total neuronal population in selected CA1/2 sectors of the hippocampus was determined. There was a significant decrease in the percentage of necrotic neurons in the central (77.5% versus 55.5%, p = 0.006) and lateral (62.5% versus 38.9%, p=0.005) areas and in the overall CA1/2 sector of the hippocampus (71.8% versus 52.2%, p = 0.008) for the 8-minute hypothermic group compared with the 8-minute normothermic group. In contrast, no differences were detected in any area of the hippocampus between the 12-minute normothermic and the 12-minute hypothermic groups (p = 0.29-0.49). Our data indicate that mild postischemic whole-body hypothermia ameliorates neuronal survival when ischemia lasts 8 minutes but not 12 minutes.