The orexigenic and ancillary pharmacologic properties of 3-carboxy-10,11-dihydrocyproheptadine (CDC) were compared to those of cyproheptadine. The threshold dose, 0.0312 mg/kg p.o., of CDC for increasing food intake in the cat is similar to that of cyproheptadine, but CDC has a broader effective dose range, extending to 8 mg/kg p.o., compared with 1 mg/kg p.o. for cyproheptadine. Using an increase in food consumption of 20% or more as the criterion of a positive response, the dose effective in 50% of the animals was 0.35 mg/kg p.o. for both CDC and cyproheptadine. Both CDC and cyproheptadine possess a long duration of appetite-stimulant action, exceeding 18 hr following 0.5 mg/kg p.o. The ancillary pharmacologic properties of CDC are considerably reduced over those of cyproheptadine, except for antihistaminic activity, CDC being about two times more potent (protection against lethality in guinea-pigs exposed to an aeosol of histamine). As an anticholinergic in mice, CDC is greater than thirteen times less active than cyproheptadine as a mydriatic agent and greater than forty-two times less potent as an antagonist of oxotremorine-induced tremors. CDC retains only about 1/25 of the antiserotonin potency of the parent compound (inhibition of serotonin-elicited edema in the rat paw and 5-hydroxytryptophan provoked head twitch in rats). CDC reduced locomotor activity in rats to a significantly lesser degree than cyproheptadine. CDC thus is a more selective agent for the therapy of anorexia.