The present study was undertaken to systematically evaluate the effect of melittin on nonstress pituitary-adrenal function of the adult female rat. In the first study rats were given melittin (0.5 mg.kg-1) or saline (0.5 ml) intraperitoneally at 0800 hr. Blood for determining plasma corticosterone levels was collected by decapitation at 4, 8, 24 or 48 hrs post-injection. Corticosterone levels of rapidly decapitated rats provided basal corticosterone levels. In general, plasma corticosterone levels of melittin-treated animals were higher than those of saline-injected rats at 4, 24, and 48 hrs but significant differences (p less than 0.05) occurred only at 4 and 48 hrs. A second study showed the melittin-evoked corticosterone response to be present at 3 days but by 6 days the response was absent. However, the duration of the increase in plasma corticosterone levels was extended to 8 days by using a double injection protocol (0.5mg.kg-1 melittin on day 1 and day 4). In all studies melittin-evoked increases in corticosterone levels were observed only in the AM and the melittin-induced increases in plasma corticosterone levels were suppressed with dexamethasone (DECADRON, 100 micrograms.kg-1, s.c.). These data indicate that a 0.5mg.kg-1 dose of melittin evokes a significant increase in adrenocortical activity and the evoked response is feedback sensitive.