The immunological response to the administration of various C-19 steroids has been of increasing interest. Although the action of dehydroepiandrosterone has been studied, the responses to its metabolites have not been explored. In the present study the ability of dehydroepiandrosterone, its conjugates, and metabolites to oppose the anti-inflammatory action of glucocorticoids on the inflammatory response to 2,4-dinitrochlorobenzene in the sensitized mouse was examined. A clear difference was seen between the antiglucocorticoid activity of dehydroepiandrosterone, its conjugates, and its 5 beta-metabolites on the one hand and the planar 5 alpha- and delta 4-metabolites, which were devoid of antiglucocorticoid activity. The mechanism of this antiglucocorticoid activity remains to be established.