Hippocampal concentrations of serotonin (5-HT) increase over the first two weeks of life, and show a peak on day 14. This pattern is very similar to the previously reported developmental changes in hippocampal type II corticosteroid receptor binding. We found that adult animals treated during the first days of life with the 5-HT neurotoxin, 5.7-dihydroxytryptamine, showed reduced hippocampal type II corticosteroid receptor binding. In addition, manipulations that resulted in increased hippocampal type II corticosteroid receptor binding, such as neonatal handling or exogenous thyroid hormone treatment also increased hippocampal 5-HT turnover. Finally, concurrent administration of the 5-HT2 receptor antagonist, ketanserin, blocked the effects of handling on hippocampal type II corticosteroid receptor binding. Taken together with the results of recent in vitro experiments, these data suggest that (a) 5-HT may be involved in the ontogenetic variation in hippocampal type II corticosteroid receptor binding, and (b) that increases in 5-HT activity may mediate the effects of environmental stimulation on hippocampal type II corticosteroid receptor binding.