AbstractThe disposition of diphenhydramine (I) and four of its ring substituted analogues, 4‐bromodiphenhydramine (II), 4‐methyldiphenhydramine (III), 2‐methyldiphen‐hydramine (IV), and 4‐t‐butyldiphenhydramine (V), was investigated in the rabbit, during and after intravenous infusion.The concentration of each analogue was determined by gas‐liquid chromatography (GLC) and the disposition parameters of clearance, volume of distribution, and elimination rate constant determined. These parameters were found to vary within the series, clearance increased in the order I